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Journal articles on the topic 'Muscles Genes'
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1
Hooper, Scott L., and Jeffrey B. Thuma. "Invertebrate Muscles: Muscle Specific Genes and Proteins." Physiological Reviews 85, no. 3 (July 2005): 1001–60. http://dx.doi.org/10.1152/physrev.00019.2004.
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This is the first of a projected series of canonic reviews covering all invertebrate muscle literature prior to 2005 and covers muscle genes and proteins except those involved in excitation-contraction coupling (e.g., the ryanodine receptor) and those forming ligand- and voltage-dependent channels. Two themes are of primary importance. The first is the evolutionary antiquity of muscle proteins. Actin, myosin, and tropomyosin (at least, the presence of other muscle proteins in these organisms has not been examined) exist in muscle-like cells in Radiata, and almost all muscle proteins are present across Bilateria, implying that the first Bilaterian had a complete, or near-complete, complement of present-day muscle proteins. The second is the extraordinary diversity of protein isoforms and genetic mechanisms for producing them. This rich diversity suggests that studying invertebrate muscle proteins and genes can be usefully applied to resolve phylogenetic relationships and to understand protein assembly coevolution. Fully achieving these goals, however, will require examination of a much broader range of species than has been heretofore performed.
2
Kostrominova, Tatiana Y., Douglas E. Dow, Robert G. Dennis, Richard A. Miller, and John A. Faulkner. "Comparison of gene expression of 2-mo denervated, 2-mo stimulated-denervated, and control rat skeletal muscles." Physiological Genomics 22, no. 2 (July 14, 2005): 227–43. http://dx.doi.org/10.1152/physiolgenomics.00210.2004.
Full textAbstract:
Loss of innervation in skeletal muscles leads to degeneration, atrophy, and loss of force. These dramatic changes are reflected in modifications of the mRNA expression of a large number of genes. Our goal was to clarify the broad spectrum of molecular events associated with long-term denervation of skeletal muscles. A microarray study compared gene expression profiles of 2-mo denervated and control extensor digitorum longus (EDL) muscles from 6-mo-old rats. The study identified 121 genes with increased and 7 genes with decreased mRNA expression. The expression of 107 of these genes had not been identified previously as changed after denervation. Many of the genes identified were genes that are highly expressed in skeletal muscles during embryonic development, downregulated in adults, and upregulated after denervation of muscle fibers. Electrical stimulation of denervated muscles preserved muscle mass and maximal force at levels similar to those in the control muscles. To understand the processes underlying the effect of electrical stimulation on denervated skeletal muscles, mRNA and protein expression of a number of genes, identified by the microarray study, was compared. The hypothesis was that loss of nerve action potentials and muscle contractions after denervation play the major roles in upregulation of gene expression in skeletal muscles. With electrical stimulation of denervated muscles, the expression levels for these genes were significantly downregulated, consistent with the hypothesis that loss of action potentials and/or contractions contribute to the alterations in gene expression in denervated skeletal muscles.
3
Chalupová, P., V. Dvořáková, A. Knoll, A. Stratil, H. Bartenschlager, R. Stupka, and J. Čítek. "Polymorphism, linkage mapping, and association analysis with carcass traits of four porcine candidate genes selected from gene-expression profiles of Czech Large White and Wild Boar muscles." Czech Journal of Animal Science 59, No. 3 (March 18, 2014): 116–27. http://dx.doi.org/10.17221/7291-cjas.
Full textAbstract:
Genes that are expressed in skeletal muscles may play a role in prenatal muscle development and postnatal muscle growth and can be considered candidates for economically important traits. Four porcine genes that were differentially expressed in skeletal muscles of Czech Large White and Wild Boar (SORT1, EMP3, IL18, and BTG2) were selected to search for polymorphism, linkage assignment, and association analysis with carcass traits. Through comparative sequencing of portions of the genes numerous polymorphisms were revealed (SORT1 – 21, EMP3 – 6, IL18 – 41, BTG2 – 9). Linkage analysis in a Meishan × Pietrain F<sub>2</sub> pedigree showed the positions of the genes relative to other genes and markers on the respective chromosomes – SORT1 on SSC4, EMP3 on SSC6, IL18 and BTG2 on SSC9. Preliminary association analysis in pig commercial crosses with selected SNPs showed associations with several carcass traits at nominal P value of < 0.05, which may indicate their involvement in muscle growth and fat deposition. The tested polymorphisms may not be causal for the associations, but they may be in linkage disequilibrium with causative mutations.
4
Lowe, Dawn A., Troy Lund, and Stephen E. Alway. "Hypertrophy-stimulated myogenic regulatory factor mRNA increases are attenuated in fast muscle of aged quails." American Journal of Physiology-Cell Physiology 275, no. 1 (July 1, 1998): C155—C162. http://dx.doi.org/10.1152/ajpcell.1998.275.1.c155.
Full textAbstract:
Myogenic regulatory factors (MRFs) are a family of skeletal muscle-specific transcription factors that regulate the expression of several muscle genes. This study was designed to determine whether MRF transcripts were increased in hypertrophy-stimulated muscle of adult quails and whether equivalent increases occurred in muscles of older quails. Slow-tonic anterior latissimus dorsi and fast-twitch patagialis muscles of adult, middle-aged, aged, and senescent quails were stretch overloaded for 6, 24, or 72 h, with contralateral muscles serving as controls. RNase protection assays showed that MRF4 and MyoD transcript levels were increased and myogenin and Myf5 transcripts were induced in stretch-overloaded muscles. However, MRF4 and MyoD increases were significantly attenuated in patagialis muscles of older quails. RT-PCR analyses of three MRF-regulated genes showed that increases in the transcription of these genes occurred with stretch overload, but the increases were less in muscles of older quails. In summary, attenuated MRF responses in muscles from aged animals may partially explain why muscles from older animals do not hypertrophy to the same extent as muscles from younger animals.
5
Raffaello, Anna, Paolo Laveder, Chiara Romualdi, Camilla Bean, Luana Toniolo, Elena Germinario, Aram Megighian, Daniela Danieli-Betto, Carlo Reggiani, and Gerolamo Lanfranchi. "Denervation in murine fast-twitch muscle: short-term physiological changes and temporal expression profiling." Physiological Genomics 25, no. 1 (March 13, 2006): 60–74. http://dx.doi.org/10.1152/physiolgenomics.00051.2005.
Full textAbstract:
Denervation deeply affects muscle structure and function, the alterations being different in slow and fast muscles. Because the effects of denervation on fast muscles are still controversial, and high-throughput studies on gene expression in denervated muscles are lacking, we studied gene expression during atrophy progression following denervation in mouse tibialis anterior (TA). The sciatic nerve was cut close to trochanter in adult CD1 mice. One, three, seven, and fourteen days after denervation, animals were killed and TA muscles were dissected out and utilized for physiological experiments and gene expression studies. Target cDNAs from TA muscles were hybridized on a dedicated cDNA microarray of muscle genes. Seventy-one genes were found differentially expressed. Microarray results were validated, and the expression of relevant genes not probed on our array was monitored by real-time quantitative PCR (RQ-PCR). Nuclear- and mitochondrial-encoded genes implicated in energy metabolism were consistently downregulated. Among genes implicated in muscle contraction (myofibrillar and sarcoplasmic reticulum), genes typical of fast fibers were downregulated, whereas those typical of slow fibers were upregulated. Electrophoresis and Western blot showed less pronounced changes in myofibrillar protein expression, partially confirming changes in gene expression. Isometric tension of skinned fibers was little affected by denervation, whereas calcium sensitivity decreased. Functional studies in mouse extensor digitorum longus muscle showed prolongation in twitch time parameters and shift to the left in force-frequency curves after denervation. We conclude that, if studied at the mRNA level, fast muscles appear not less responsive than slow muscles to the interruption of neural stimulation.
6
Hitachi, Keisuke, Masashi Nakatani, and Kunihiro Tsuchida. "Long Non-Coding RNA Myoparr Regulates GDF5 Expression in Denervated Mouse Skeletal Muscle." Non-Coding RNA 5, no. 2 (April 8, 2019): 33. http://dx.doi.org/10.3390/ncrna5020033.
Full textAbstract:
Skeletal muscle is a highly plastic tissue and decreased skeletal muscle mass (muscle atrophy) results in deteriorated motor function and perturbed body homeostasis. Myogenin promoter-associated long non-coding RNA (lncRNA) Myoparr promotes skeletal muscle atrophy caused by surgical denervation; however, the precise molecular mechanism remains unclear. Here, we examined the downstream genes of Myoparr during muscle atrophy following denervation of tibialis anterior (TA) muscles in C57BL/6J mice. Myoparr knockdown affected the expression of 848 genes. Sixty-five of the genes differentially regulated by Myoparr knockdown coded secretory proteins. Among these 65 genes identified in Myoparr-depleted skeletal muscles after denervation, we focused on the increased expression of growth/differentiation factor 5 (GDF5), an inhibitor of muscle atrophy. Myoparr knockdown led to activated bone morphogenetic protein (BMP) signaling in denervated muscles, as indicated by the increased levels of phosphorylated Smad1/5/8. Our detailed evaluation of downstream genes of Myoparr also revealed that Myoparr regulated differential gene expression between myogenic differentiation and muscle atrophy. This is the first report demonstrating the in vivo role of Myoparr in regulating BMP signaling in denervated muscles. Therefore, lncRNAs that have inhibitory activity on BMP signaling may be putative therapeutic targets for skeletal muscle atrophy.
7
Glenmark, Birgitta, Maria Nilsson, Hui Gao, Jan-Åke Gustafsson, Karin Dahlman-Wright, and Håkan Westerblad. "Difference in skeletal muscle function in males vs. females: role of estrogen receptor-β." American Journal of Physiology-Endocrinology and Metabolism 287, no. 6 (December 2004): E1125—E1131. http://dx.doi.org/10.1152/ajpendo.00098.2004.
Full textAbstract:
Male skeletal muscles are generally faster and have higher maximum power output than female muscles. Conversely, during repeated contractions, female muscles are generally more fatigue resistant and recover faster. We studied the role of estrogen receptor-β (ERβ) in this gender difference by comparing contractile function of soleus (mainly slow-twitch) and extensor digitorum longus (fast-twitch) muscles isolated from ERβ-deficient (ERβ−/−) and wild-type mice of both sexes. Results showed generally shorter contraction and relaxation times in male compared with female muscles, and ERβ deficiency had no effect on this. Fatigue (induced by repeated tetanic contractions) and recovery of female muscles were not affected by ERβ deficiency. However, male ERβ−/− muscles were slightly more fatigue resistant and produced higher forces during the recovery period than wild-type male muscles. In fact, female muscles and male ERβ−/− muscles displayed markedly better recovery than male wild-type muscles. Gene screening of male soleus muscles showed 25 genes that were differently expressed in ERβ−/− and wild-type mice. Five of these genes were selected for further analysis: muscle ankyrin repeat protein-2, muscle LIM protein, calsequestrin, parvalbumin, and aquaporin-1. Expression of these genes showed a similar general pattern: increased expression in male and decreased expression in female ERβ−/− muscles. In conclusion, ERβ deficiency results in increased performance during fatigue and recovery of male muscles, whereas female muscles are not affected. Improved contractile performance of male ERβ−/− mouse muscles was associated with increased expression of mRNAs encoding important muscle proteins.
8
Depuydt, Christophe E., Veerle Goosens, Rekin’s Janky, Ann D’Hondt, Jan L. De Bleecker, Nathalie Noppe, Stefaan Derveaux, Dietmar R. Thal, and Kristl G. Claeys. "Unraveling the Molecular Basis of the Dystrophic Process in Limb-Girdle Muscular Dystrophy LGMD-R12 by Differential Gene Expression Profiles in Diseased and Healthy Muscles." Cells 11, no. 9 (April 30, 2022): 1508. http://dx.doi.org/10.3390/cells11091508.
Full textAbstract:
Limb-girdle muscular dystrophy R12 (LGMD-R12) is caused by two mutations in anoctamin-5 (ANO5). Our aim was to identify genes and pathways that underlie LGMD-R12 and explain differences in the molecular predisposition and susceptibility between three thigh muscles that are severely (semimembranosus), moderately (vastus lateralis) or mildly (rectus femoris) affected in this disease. We performed transcriptomics on these three muscles in 16 male LGMD-R12 patients and 15 age-matched male controls. Our results showed that LGMD-R12 dystrophic muscle is associated with the expression of genes indicative of fibroblast and adipocyte replacement, such as fibroadipogenic progenitors and immune cell infiltration, while muscle protein synthesis and metabolism were downregulated. Muscle degeneration was associated with an increase in genes involved in muscle injury and inflammation, and muscle repair/regeneration. Baseline differences between muscles in healthy individuals indicated that muscles that are the most affected by LGMD-R12 have the lowest expression of transcription factor networks involved in muscle (re)generation and satellite stem cell activation. Instead, they show relative high levels of fetal/embryonic myosins, all together indicating that muscles differ in their baseline regenerative potential. To conclude, we profiled the gene expression landscape in LGMD-R12, identified baseline differences in expression levels between differently affected muscles and characterized disease-associated changes.
9
Agarwal, Andrea B., Austin J. Christensen, Cheng-Yuan Feng, Dan Wen, L. Alan Johnson, and Christopher S. von Bartheld. "Expression of schizophrenia biomarkers in extraocular muscles from patients with strabismus: an explanation for the link between exotropia and schizophrenia?" PeerJ 5 (December 22, 2017): e4214. http://dx.doi.org/10.7717/peerj.4214.
Full textAbstract:
Recent studies have implicated exotropia as a risk factor for schizophrenia. We determined whether schizophrenia biomarkers have abnormal levels of expression in extraocular muscles from patients with strabismus and explored whether differences in gene expression between medial and lateral rectus muscles may explain the specific association of schizophrenia with exotropia but not esotropia. Samples from horizontal extraocular muscles were obtained during strabismus surgery and compared with age- and muscle type-matched normal muscles from organ donors. We used PCR arrays to identify differences in gene expression among 417 signaling molecules. We then focused on established schizophrenia-related growth factors, cytokines, and regulators of the extracellular matrix. Among 36 genes with significantly altered gene expression in dysfunctional horizontal rectus muscles, over one third were schizophrenia-related: CTGF, CXCR4, IL1B, IL10RA, MIF, MMP2, NPY1R, NRG1, NTRK2, SERPINA3, TIMP1, TIMP2, and TNF (adjusted p value ≤ 0.016667). By PCR array, expression of three of these genes was significantly different in medial rectus muscles, while eleven were significantly altered in lateral rectus muscles. Comparing baseline levels between muscle types, three schizophrenia-related genes (NPY1R, NTRK2, TIMP2) had lower levels of expression in medial rectus muscles. Despite the surprisingly large number of schizophrenia-related genes with altered gene expression levels in dysfunctional muscles, the lack of specificity for medial rectus muscles undermines a model of shared, region-specific gene expression abnormalities between exotropia and schizophrenia, but rather suggests consideration of the alternative model: that exotropia-induced aberrant early visual experiences may enable and/or contribute as a causative factor to the development of schizophrenia.
10
Rouger, Karl, Martine Le Cunff, Marja Steenman, Marie-Claude Potier, Nathalie Gibelin, Claude A. Dechesne, and Jean J. Leger. "Global/temporal gene expression in diaphragm and hindlimb muscles of dystrophin-deficient (mdx) mice." American Journal of Physiology-Cell Physiology 283, no. 3 (September 1, 2002): C773—C784. http://dx.doi.org/10.1152/ajpcell.00112.2002.
Full textAbstract:
The mdx mouse is a model for human Duchenne muscular dystrophy (DMD), an X-linked degenerative disease of skeletal muscle tissue characterized by the absence of the dystrophin protein. The mdx mice display a much milder phenotype than DMD patients. After the first week of life when all mdx muscles evolve like muscles of young DMD patients, mdx hindlimb muscles substantially compensate for the lack of dystrophin, whereas mdx diaphragm muscle becomes progressively affected by the disease. We used cDNA microarrays to compare the expression profile of 1,082 genes, previously selected by a subtractive method, in control and mdx hindlimb and diaphragm muscles at 12 time points over the first year of the mouse life. We determined that 1) the dystrophin gene defect induced marked expression remodeling of 112 genes encoding proteins implicated in diverse muscle cell functions and 2) two-thirds of the observed transcriptomal anomalies differed between adult mdx hindlimb and diaphragm muscles. Our results showed that neither mdx diaphram muscle nor mdx hindlimb muscles evolve entirely like the human DMD muscles. This finding should be taken under consideration for the interpretation of future experiments using mdx mice as a model for therapeutic assays.
11
Chen, Ting, Timothy M. Moore, Mark T. W. Ebbert, Natalie L. McVey, Steven R. Madsen, David M. Hallowell, Alexander M. Harris, et al. "Liver kinase B1 inhibits the expression of inflammation-related genes postcontraction in skeletal muscle." Journal of Applied Physiology 120, no. 8 (April 15, 2016): 876–88. http://dx.doi.org/10.1152/japplphysiol.00727.2015.
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Skeletal muscle-specific liver kinase B1 (LKB1) knockout mice (skmLKB1-KO) exhibit elevated mitogen-activated protein kinase (MAPK) signaling after treadmill running. MAPK activation is also associated with inflammation-related signaling in skeletal muscle. Since exercise can induce muscle damage, and inflammation is a response triggered by damaged tissue, we therefore hypothesized that LKB1 plays an important role in dampening the inflammatory response to muscle contraction, and that this may be due in part to increased susceptibility to muscle damage with contractions in LKB1-deficient muscle. Here we studied the inflammatory response and muscle damage with in situ muscle contraction or downhill running. After in situ muscle contractions, the phosphorylation of both NF-κB and STAT3 was increased more in skmLKB1-KO vs. wild-type (WT) muscles. Analysis of gene expression via microarray and RT-PCR shows that expression of many inflammation-related genes increased after contraction only in skmLKB1-KO muscles. This was associated with mild skeletal muscle fiber membrane damage in skmLKB1-KO muscles. Gene markers of oxidative stress were also elevated in skmLKB1-KO muscles after contraction. Using the downhill running model, we observed significantly more muscle damage after running in skmLKB1-KO mice, and this was associated with greater phosphorylation of both Jnk and STAT3 and increased expression of SOCS3 and Fos. In conclusion, we have shown that the lack of LKB1 in skeletal muscle leads to an increased inflammatory state in skeletal muscle that is exacerbated by muscle contraction. Increased susceptibility of the muscle to damage may underlie part of this response.
12
Walker, Rebecca L., Joseph R. Hume, and Burton Horowitz. "Differential expression and alternative splicing of TRP channel genes in smooth muscles." American Journal of Physiology-Cell Physiology 280, no. 5 (May 1, 2001): C1184—C1192. http://dx.doi.org/10.1152/ajpcell.2001.280.5.c1184.
Full textAbstract:
Nonselective cation channels (NSCC) are targets of excitatory agonists in smooth muscle, representing the nonselective cation current I cat. Na+ influx through NSCC causes depolarizations and activates voltage-dependent Ca2+ channels, resulting in contraction. The molecular identity of I cat in smooth muscle has not been elucidated; however, products of the transient receptor potential (TRP) genes have characteristics similar to native I cat. We have determined the levels of TRP transcriptional expression in several murine and canine gastrointestinal and vascular smooth muscles and have analyzed the alternative processing of these transcripts. Of the seven TRP gene family members, transcripts for TRP4, TRP6, and TRP7 were detected in all murine and canine smooth muscle cell preparations. TRP3 was detected only in canine renal artery smooth muscle cells. The full-length cDNAs for TRP4, TRP6, and TRP7, as well as one splice variant of TRP4 and two splice variants of TRP7, were cloned from murine colonic smooth muscle. Quantitative RT-PCR determined the relative amounts of TRP4, TRP6, and TRP7 transcripts, as well as that of the splice variants, in several murine smooth muscles. TRP4 is the most highly expressed, while TRP6 and TRP7 are expressed at a lower level in the same tissues. Splice variants for TRP7, deleted for exons encoding amino acids including transmembrane segment S1, predominated in murine smooth muscles, while the full-length form of the transcript was expressed in canine smooth muscles.
13
Gomez Ruiz, M., and M. Bate. "Segregation of myogenic lineages in Drosophila requires numb." Development 124, no. 23 (December 1, 1997): 4857–66. http://dx.doi.org/10.1242/dev.124.23.4857.
Full textAbstract:
Terminal divisions of myogenic lineages in the Drosophila embryo generate sibling myoblasts that found larval muscles or form precursors of adult muscles. Alternative fates adopted by sibling myoblasts are associated with distinct patterns of gene expression. Genes expressed in the progenitor cell are maintained in one sibling and repressed in the other. These differences depend on an asymmetric segregation of Numb between sibling cells. In numb mutants, muscle fates associated with repression are duplicated and alternative muscles are lost. If numb is overexpressed the reverse transformation occurs. Numb acts to block Notch-mediated repression of genes expressed in muscle progenitor cells. Thus asymmetric cell divisions are essential determinants of muscle fates during myogenesis in Drosophila
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Plenefisch, J. D., X. Zhu, and E. M. Hedgecock. "Fragile skeletal muscle attachments in dystrophic mutants of Caenorhabditis elegans: isolation and characterization of the mua genes." Development 127, no. 6 (March 15, 2000): 1197–207. http://dx.doi.org/10.1242/dev.127.6.1197.
Full textAbstract:
Over 30 Caenorhabditis elegans mutants were identified with normal muscle differentiation and initial locomotion followed by catastrophic detachment of skeletal muscles from the body wall. Reducing the strength of muscle contraction in these mutants with a myosin gene mutation suppresses muscle detachment. These dystrophic mutants identify a novel class of genes required for growth and maintenance of functional muscle attachments, not exceptional alleles of genes required for muscle differentiation and contractility. Nine new genes, named mua, and two previously published loci, unc-23 and vab-10, cause fragile musscle attachments. The primary sites of muscle detachment, including the plane of tissue separation, are characteristic for each gene. We suggest these genes identify feedback mechanisms whereby local strain regulates the extent of myofibril contraction and the placement of new muscle attachments in functioning muscles. Finally, we draw some comparisons to vertebrate skin fragility diseases and muscular dystrophies.
15
Zhao, Xiuhui, Junning Ye, Xunkai Lin, Huiwen Xue, Xian Zou, Guangbin Liu, Ming Deng, et al. "Identification of Key Functional Genes and LncRNAs Influencing Muscle Growth and Development in Leizhou Black Goats." Genes 14, no. 4 (April 8, 2023): 881. http://dx.doi.org/10.3390/genes14040881.
Full textAbstract:
Meat yield and quality are important economic traits of livestock. Herein, longissimus dorsi (LD) muscles of Leizhou black goats aged 0, 3, and 6 months were used to identify differentially expressed messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) by high-throughput RNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to analyze differentially expressed genes. Expression levels of regulator of calcineurin 1 (RCAN1) and olfactory receptor 2AP1 (OR2AP1) were significantly different in LD muscles of goats aged 0, 3, and 6 months, indicating potentially important roles in postnatal muscle development. Differentially expressed lncRNAs and mRNAs were mainly enriched in biological processes and pathways related to cellular energy metabolism, consistent with previous studies. Three lncRNAs, TCONS_00074191, TCONS_00074190, and TCONS_00078361, may play a cis-acting role with methyltransferase-like 11B (METTL11B) genes and participate in the methylation of goat muscle proteins. Some of the identified genes may provide valuable resources for future studies on postnatal meat development in goat muscles.
16
Welle, Stephen, Andrew Cardillo, Michelle Zanche, and Rabi Tawil. "Skeletal muscle gene expression after myostatin knockout in mature mice." Physiological Genomics 38, no. 3 (August 2009): 342–50. http://dx.doi.org/10.1152/physiolgenomics.00054.2009.
Full textAbstract:
There is much interest in developing anti-myostatin agents to reverse or prevent muscle atrophy in adults, so it is important to characterize the effects of reducing myostatin activity after normal muscle development. For assessment of the effect of loss of myostatin signaling on gene expression in muscle, RNA from mice with postdevelopmental myostatin knockout was analyzed with oligonucleotide microarrays. Myostatin was undetectable in muscle within 2 wk after Cre recombinase activation in 4-month-old male mice with floxed myostatin genes. Three months after myostatin depletion, muscle mass had increased 26% (vs. 2% after induction of Cre activity in mice with normal myostatin genes), at which time the expression of several hundred genes differed in knockout and control mice at nominal P < 0.01. In contrast to previously reported effects of constitutive myostatin knockout, postdevelopmental knockout did not downregulate expression of genes encoding slow isoforms of contractile proteins or genes encoding proteins involved in energy metabolism. Several collagen genes were expressed at 20–50% lower levels in the myostatin-deficient muscles, which had ∼25% less collagen than normal muscles as reflected by hydroxyproline content. Most of the other genes affected by myostatin depletion have not been previously linked to myostatin signaling. Gene set enrichment analysis suggested that Smads are not the only transcription factors with reduced activity after myostatin depletion. These data reinforce other evidence that myostatin regulates collagen production in muscle and demonstrate that many of the previously reported effects of constitutive myostatin deficiency do not occur when myostatin is knocked out in mature muscles.
17
Buckingham, Margaret. "Gene regulatory networks and cell lineages that underlie the formation of skeletal muscle." Proceedings of the National Academy of Sciences 114, no. 23 (June 5, 2017): 5830–37. http://dx.doi.org/10.1073/pnas.1610605114.
Full textAbstract:
Skeletal muscle in vertebrates is formed by two major routes, as illustrated by the mouse embryo. Somites give rise to myogenic progenitors that form all of the muscles of the trunk and limbs. The behavior of these cells and their entry into the myogenic program is controlled by gene regulatory networks, where paired box gene 3 (Pax3) plays a predominant role. Head and some neck muscles do not derive from somites, but mainly form from mesoderm in the pharyngeal region. Entry into the myogenic program also depends on the myogenic determination factor (MyoD) family of genes, but Pax3 is not expressed in these myogenic progenitors, where different gene regulatory networks function, with T-box factor 1 (Tbx1) and paired-like homeodomain factor 2 (Pitx2) as key upstream genes. The regulatory genes that underlie the formation of these muscles are also important players in cardiogenesis, expressed in the second heart field, which is a major source of myocardium and of the pharyngeal arch mesoderm that gives rise to skeletal muscles. The demonstration that both types of striated muscle derive from common progenitors comes from clonal analyses that have established a lineage tree for parts of the myocardium and different head and neck muscles. Evolutionary conservation of the two routes to skeletal muscle in vertebrates extends to chordates, to trunk muscles in the cephlochordate Amphioxus and to muscles derived from cardiopharyngeal mesoderm in the urochordate Ciona, where a related gene regulatory network determines cardiac or skeletal muscle cell fates. In conclusion, Eric Davidson’s visionary contribution to our understanding of gene regulatory networks and their evolution is acknowledged.
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Li, Yanying, Hehe Liu, Lei Wang, Yang Xi, Jiwen Wang, Rongping Zhang, Liang Li, Lili Bai, and Ahsan Mustafa. "Evidence Supporting the Regulatory Relationships through a Paracrine Pathway between the Sternum and Pectoral Muscles in Ducks." Genes 12, no. 4 (March 24, 2021): 463. http://dx.doi.org/10.3390/genes12040463.
Full textAbstract:
Muscles and bones are anatomically closely linked, and they can conduct communication by mechanical and chemical signals. However, the specific regulatory mechanism between the pectoral muscle and sternum in birds was largely unknown. The present study explored the potential relationship between them in ducks. The result of the sections showed that more nuclei in proliferate states were observed in the pectoral muscle fibers attached to the calcified sternum, than those attached to the un-calcified sternum. The RNA-seq identified 328 differentially expressed genes (DEGs) in the sternum between the calcified and un-calcified groups. Gene ontology (GO) showed that the DEGs were mainly enriched in pathways associated with calcification. In addition, DEGs in the muscles between the calcified and un-calcified sternum groups were mainly annotated to signal transduction receptor pathways. The expression patterns of genes encoding for secreted proteins, in bone (CXCL12, BMP7 and CTSK) and muscle (LGI1), were clustered with muscle development (MB) and bone calcification (KCNA1, OSTN, COL9A3, and DCN) related genes, respectively, indicating the regulatory relationships through a paracrine pathway existing between the sternum and pectoral muscles in ducks. Together, we demonstrated that the pectoral muscle development was affected by the sternal ossification states in ducks. The VEGFA, CXCL12, SPP1, NOG, and BMP7 were possibly the key genes to participate in the ossification of the duck sternum. We firstly listed evidence supporting the regulatory relationships through a paracrine pathway between the sternum and pectoral muscles in ducks, which provided scientific data for the study of the synergistic development of bone and skeletal muscle.
19
Yoshioka, Kiyoshi, Hiroshi Nagahisa, Fumihito Miura, Hiromitsu Araki, Yasutomi Kamei, Yasuo Kitajima, Daiki Seko, et al. "Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle." Science Advances 7, no. 24 (June 2021): eabd7924. http://dx.doi.org/10.1126/sciadv.abd7924.
Full textAbstract:
Muscle stem cells (satellite cells) are distributed throughout the body and have heterogeneous properties among muscles. However, functional topographical genes in satellite cells of adult muscle remain unidentified. Here, we show that expression of Homeobox-A (Hox-A) cluster genes accompanied with DNA hypermethylation of the Hox-A locus was robustly maintained in both somite-derived muscles and their associated satellite cells in adult mice, which recapitulates their embryonic origin. Somite-derived satellite cells were clearly separated from cells derived from cranial mesoderm in Hoxa10 expression. Hoxa10 inactivation led to genomic instability and mitotic catastrophe in somite-derived satellite cells in mice and human. Satellite cell–specific Hoxa10 ablation in mice resulted in a decline in the regenerative ability of somite-derived muscles, which were unobserved in cranial mesoderm–derived muscles. Thus, our results show that Hox gene expression profiles instill the embryonic history in satellite cells as positional memory, potentially modulating region-specific pathophysiology in adult muscles.
20
Sawano, Shoko, Misaki Fukushima, Taiki Akasaka, Mako Nakamura, Ryuichi Tatsumi, Yoshihide Ikeuchi, and Wataru Mizunoya. "Up- and Downregulated Genes after Long-Term Muscle Atrophy Induced by Denervation in Mice Detected Using RNA-Seq." Life 13, no. 5 (April 29, 2023): 1111. http://dx.doi.org/10.3390/life13051111.
Full textAbstract:
Skeletal muscle atrophy occurs rapidly as a result of inactivity. Although there are many reports on changes in gene expression during the early phase of muscle atrophy, the patterns of up-and downregulated gene expression after long-term and equilibrated muscle atrophy are poorly understood. In this study, we comprehensively examined the changes in gene expression in long-term denervated mouse muscles using RNA-Seq. The murine right sciatic nerve was denervated, and the mice were housed for five weeks. The cross-sectional areas of the hind limb muscles were measured using an X-ray CT system 35 days after denervation. After 28 d of denervation, the cross-sectional area of the muscle decreased to approximately 65% of that of the intact left muscle and reached a plateau. Gene expression in the soleus and extensor digitorum longus (EDL) muscles on the 36th day was analyzed using RNA-Seq and validated using RT-qPCR. RNA-Seq analysis revealed that three genes—Adora1, E230016M11Rik, and Gm10718—were upregulated and one gene—Gm20515—was downregulated in the soleus muscle; additionally, four genes—Adora1, E230016M11Rik, Pigh, and Gm15557—were upregulated and one gene—Fzd7—was downregulated in the EDL muscle (FDR < 0.05). Among these genes, E230016M11Rik, one of the long non-coding RNAs, was significantly upregulated in both the muscles. These findings indicate that E230016M11Rik could be a candidate gene for the maintenance of atrophied skeletal muscle size and an atrophic state.
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Evans, Marianna, Kevin Morine, Cyelee Kulkarni, and Elisabeth R. Barton. "Expression profiling reveals heightened apoptosis and supports fiber size economy in the murine muscles of mastication." Physiological Genomics 35, no. 1 (September 2008): 86–95. http://dx.doi.org/10.1152/physiolgenomics.00232.2007.
Full textAbstract:
Distinctions between craniofacial and axial muscles exist from the onset of development and throughout adulthood. The masticatory muscles are a specialized group of craniofacial muscles that retain embryonic fiber properties in the adult, suggesting that the developmental origin of these muscles may govern a pattern of expression that differs from limb muscles. To determine the extent of these differences, expression profiling of total RNA isolated from the masseter and tibialis anterior (TA) muscles of adult female mice was performed, which identified transcriptional changes in unanticipated functional classes of genes in addition to those attributable to fiber type. In particular, the masseters displayed a reduction of transcripts associated with contractile and cytoskeletal load-sensing and anabolic processes, and heightened expression of genes associated with stress. Associated with these observations was a significantly smaller fiber cross-sectional area in masseters, significantly elevated load-sensing signaling (phosphorylated focal adhesion kinase), and increased apoptotic index in masseters compared with TA muscles. Based on these results, we hypothesize that masticatory muscles may have a fundamentally different strategy for muscle design, compared with axial muscles. Specifically there are small diameter fibers that have an attenuated ability to hypertrophy, but an increased propensity to undergo apoptosis. These results may provide insight into the molecular basis for specific muscle-related pathologies associated with masticatory muscles.
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Barchi, Robert L. "Bad channel genes and weak muscles." Current Biology 1, no. 3 (June 1991): 150–52. http://dx.doi.org/10.1016/0960-9822(91)90216-j.
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Wang, Huan, Busu Li, Long Yang, Chen Jiang, Tao Zhang, Shufang Liu, and Zhimeng Zhuang. "Expression profiles and transcript properties of fast-twitch and slow-twitch muscles in a deep-sea highly migratory fish, Pseudocaranx dentex." PeerJ 10 (March 30, 2022): e12720. http://dx.doi.org/10.7717/peerj.12720.
Full textAbstract:
Fast-twitch and slow-twitch muscles are the two principal skeletal muscle types in teleost with obvious differences in metabolic and contractile phenotypes. The molecular mechanisms that control and maintain the different muscle types remain unclear yet. Pseudocaranx dentex is a highly mobile active pelagic fish with distinctly differentiated fast-twitch and slow-twitch muscles. Meanwhile, P. dentex has become a potential target species for deep-sea aquaculture because of its considerable economic value. To elucidate the molecular characteristics in the two muscle types of P. dentex, we generated 122 million and 130 million clean reads from fast-twitch and slow-witch muscles using RNA-Seq, respectively. Comparative transcriptome analysis revealed that 2,862 genes were differentially expressed. According to GO and KEGG analysis, the differentially expressed genes (DEGs) were mainly enriched in energy metabolism and skeletal muscle structure related pathways. Difference in the expression levels of specific genes for glycolytic and lipolysis provided molecular evidence for the differences in energy metabolic pathway between fast-twitch and slow-twitch muscles of P. dentex. Numerous genes encoding key enzymes of mitochondrial oxidative phosphorylation pathway were significantly upregulated at the mRNA expression level suggested slow-twitch muscle had a higher oxidative phosphorylation to ensure more energy supply. Meanwhile, expression patterns of the main skeletal muscle developmental genes were characterized, and the expression signatures of Sox8, Myod1, Calpain-3, Myogenin, and five insulin-like growth factors indicated that more myogenic cells of fast-twitch muscle in the differentiating state. The analysis of important skeletal muscle structural genes showed that muscle type-specific expression of myosin, troponin and tropomyosin may lead to the phenotypic structure differentiation. RT-qPCR analysis of twelve DEGs showed a good correlation with the transcriptome data and confirmed the reliability of the results presented in the study. The large-scale transcriptomic data generated in this study provided an overall insight into the thorough gene expression profiles of skeletal muscle in a highly mobile active pelagic fish, which could be valuable for further studies on molecular mechanisms responsible for the diversity and function of skeletal muscle.
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Cussonneau, Laura, Christian Boyer, Charlotte Brun, Christiane Deval, Emmanuelle Loizon, Emmanuelle Meugnier, Elise Gueret, et al. "Concurrent BMP Signaling Maintenance and TGF-β Signaling Inhibition Is a Hallmark of Natural Resistance to Muscle Atrophy in the Hibernating Bear." Cells 10, no. 8 (July 23, 2021): 1873. http://dx.doi.org/10.3390/cells10081873.
Full textAbstract:
Muscle atrophy arises from a multiplicity of physio-pathological situations and has very detrimental consequences for the whole body. Although knowledge of muscle atrophy mechanisms keeps growing, there is still no proven treatment to date. This study aimed at identifying new drivers for muscle atrophy resistance. We selected an innovative approach that compares muscle transcriptome between an original model of natural resistance to muscle atrophy, the hibernating brown bear, and a classical model of induced atrophy, the unloaded mouse. Using RNA sequencing, we identified 4415 differentially expressed genes, including 1746 up- and 2369 down-regulated genes, in bear muscles between the active versus hibernating period. We focused on the Transforming Growth Factor (TGF)-β and the Bone Morphogenetic Protein (BMP) pathways, respectively, involved in muscle mass loss and maintenance. TGF-β- and BMP-related genes were overall down- and up-regulated in the non-atrophied muscles of the hibernating bear, respectively, and the opposite occurred for the atrophied muscles of the unloaded mouse. This was further substantiated at the protein level. Our data suggest TGF-β/BMP balance is crucial for muscle mass maintenance during long-term physical inactivity in the hibernating bear. Thus, concurrent activation of the BMP pathway may potentiate TGF-β inhibiting therapies already targeted to prevent muscle atrophy.
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Harber, Matthew P., Justin D. Crane, Jared M. Dickinson, Bozena Jemiolo, Ulrika Raue, Todd A. Trappe, and Scott W. Trappe. "Protein synthesis and the expression of growth-related genes are altered by running in human vastus lateralis and soleus muscles." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 296, no. 3 (March 2009): R708—R714. http://dx.doi.org/10.1152/ajpregu.90906.2008.
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Recent evidence suggests aerobic exercise may help preserve soleus muscle mass during unloading. The purpose of this investigation was to examine the muscle-specific metabolic response to running as it relates to muscle growth. Mixed-muscle protein synthesis [fractional synthetic rate (FSR)] and gene expression (GE) were examined in the vastus lateralis (VL) and soleus (SOL) muscles from eight men (26 ± 2 yr; V̇o2max 63 ± 2 ml·kg−1·min−1) before and after a 45-min level-grade treadmill run at 77 ± 1% intensity. Muscle glycogen utilization was similar between muscles. Resting FSR was similar between the VL (0.080 ± 0.007 %/h) and SOL (0.086 ± 0.008 %/h) and was higher ( P < 0.05) 24 h postexercise compared with rest for both muscles. The absolute change in FSR was not different between muscles (0.030 ± 0.007 vs. 0.037 ± 0.012 %/h for VL and SOL). At baseline, myostatin GE was approximately twofold higher ( P < 0.05) in SOL compared with VL, while no other muscle-specific differences in GE were present. After running, myostatin GE was suppressed ( P < 0.05) in both muscles at 4 h and was higher ( P < 0.05) than baseline at 24 h for VL only. Muscle regulatory factor 4 mRNA was elevated ( P < 0.05) at 4 h in both SOL and VL; MyoD and peroxisome-proliferator-activated receptor-gamma coactivator-1α (PGC-1α) were higher ( P < 0.05) at 4 h, and forkhead box [FOXO]3A was higher at 24 h in SOL only, while muscle-RING-finger protein-1 (MuRF-1) was higher ( P < 0.05) at 4 h in VL only. Myogenin and atrogin-1 GE were unaltered. The similar increases between muscles in FSR support running as part of the exercise countermeasure to preserve soleus mass during unloading. The subtle differences in GE suggest a potential mechanism for muscle-specific adaptations to chronic run training.
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Abe, Takaaki, Yu Kitaoka, Dale Manjiro Kikuchi, Kohei Takeda, Osamu Numata, and Tohru Takemasa. "High-intensity interval training-induced metabolic adaptation coupled with an increase in Hif-1α and glycolytic protein expression." Journal of Applied Physiology 119, no. 11 (December 1, 2015): 1297–302. http://dx.doi.org/10.1152/japplphysiol.00499.2015.
Full textAbstract:
It is known that repeated bouts of high-intensity interval training (HIIT) lead to enhanced levels of glycolysis, glycogenesis, and lactate transport proteins in skeletal muscle; however, little is known about the molecular mechanisms underlying these adaptations. To decipher the mechanism leading to improvement of skeletal muscle glycolytic capacity associated with HIIT, we examined the role of hypoxia-inducible factor-1α (Hif-1α), the major transcription factor regulating the expression of genes related to anaerobic metabolism, in the adaptation to HIIT. First, we induced Hif-1α accumulation using ethyl 3,4-dihydroxybenzoate (EDHB) to assess the potential role of Hif-1α in skeletal muscle. Treatment with EDHB significantly increased the protein levels of Hif-1α in gastrocnemius muscles, accompanied by elevated expression of genes related to glycolysis, glycogenesis, and lactate transport. Daily administration of EDHB for 1 wk resulted in elevated glycolytic enzyme activity in gastrocnemius muscles. Second, we examined whether a single bout of HIIT could induce Hif-1α protein accumulation and subsequent increase in the expression of genes related to anaerobic metabolism in skeletal muscle. We observed that the protein levels of Hif-1α and expression of the target genes were elevated 3 h after an acute bout of HIIT in gastrocnemius muscles. Last, we examined the effects of long-term HIIT. We found that long-term HIIT increased the basal levels of Hif-1α as well as the glycolytic capacity in gastrocnemius muscles. Our results suggest that Hif-1α is a key regulator in the metabolic adaptation to high-intensity training.
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Oas, Sandy T., Anton L. Bryantsev, and Richard M. Cripps. "Arrest is a regulator of fiber-specific alternative splicing in the indirect flight muscles of Drosophila." Journal of Cell Biology 206, no. 7 (September 22, 2014): 895–908. http://dx.doi.org/10.1083/jcb.201405058.
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Drosophila melanogaster flight muscles are distinct from other skeletal muscles, such as jump muscles, and express several uniquely spliced muscle-associated transcripts. We sought to identify factors mediating splicing differences between the flight and jump muscle fiber types. We found that the ribonucleic acid–binding protein Arrest (Aret) is expressed in flight muscles: in founder cells, Aret accumulates in a novel intranuclear compartment that we termed the Bruno body, and after the onset of muscle differentiation, Aret disperses in the nucleus. Down-regulation of the aret gene led to ultrastructural changes and functional impairment of flight muscles, and transcripts of structural genes expressed in the flight muscles became spliced in a manner characteristic of jump muscles. Aret also potently promoted flight muscle splicing patterns when ectopically expressed in jump muscles or tissue culture cells. Genetically, aret is located downstream of exd (extradenticle), hth (homothorax), and salm (spalt major), transcription factors that control fiber identity. Our observations provide insight into a transcriptional and splicing regulatory network for muscle fiber specification.
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Hildebrandt, Audrey L., and P. Darrell Neufer. "Exercise attenuates the fasting-induced transcriptional activation of metabolic genes in skeletal muscle." American Journal of Physiology-Endocrinology and Metabolism 278, no. 6 (June 1, 2000): E1078—E1086. http://dx.doi.org/10.1152/ajpendo.2000.278.6.e1078.
Full textAbstract:
Fasting elicits a progressive increase in lipid metabolism within skeletal muscle. To determine the effects of fasting on the transcriptional regulation of genes important for metabolic control in skeletal muscle composed of different fiber types, nuclei from control and fasted (24 and 72 h) rats were subjected to nuclear run-on analysis using an RT-PCR-based technique. Fasting increased ( P < 0.05) transcription rate of the muscle-specific uncoupling protein-3 gene (UCP3) 14.3- to 21.1-fold in white gastrocnemius (WG; fast-twitch glycolytic) and 5.5- to 7.5-fold in red gastrocnemius (RG; fast-twitch oxidative) and plantaris (PL; mixed) muscles. No change occurred in soleus (slow-twitch oxidative) muscle. Fasting also increased transcription rate of the lipoprotein lipase (LPL), muscle carnitine palmitoyltransferase I (CPT I), and long-chain acyl-CoA dehydrogenase (LCAD) genes 1.7- to 3.7-fold in WG, RG, and PL muscles. Transcription rate responses were similar after 24 and 72 h of fasting. Surprisingly, increasing metabolic demand during the initial 8 h of starvation (two 2-h bouts of treadmill running) attenuated the 24-h fasting-induced transcriptional activation of UCP3, LPL, CPT I, and LCAD in RG and PL muscles, suggesting the presence of opposing regulatory mechanisms. These data demonstrate that fasting elicits a fiber type-specific coordinate increase in the transcription rate of several genes involved in and/or required for lipid metabolism and indicate that exercise may attenuate the fasting-induced transcriptional activation of specific metabolic genes.
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Barash, Ilona A., Liby Mathew, Allen F. Ryan, Ju Chen, and Richard L. Lieber. "Rapid muscle-specific gene expression changes after a single bout of eccentric contractions in the mouse." American Journal of Physiology-Cell Physiology 286, no. 2 (February 2004): C355—C364. http://dx.doi.org/10.1152/ajpcell.00211.2003.
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Eccentric contractions (ECs), in which a muscle is forced to lengthen while activated, result in muscle injury and, eventually, muscle strengthening and prevention of further injury. Although the mechanical basis of EC-induced injury has been studied in detail, the biological response of muscle is less well characterized. This study presents the development of a minimally invasive model of EC injury in the mouse, follows the time course of torque recovery after an injurious bout of ECs, and uses Affymetrix microarrays to compare the gene expression profile 48 h after ECs to both isometrically stimulated muscles and contralateral muscles. Torque dropped by ∼55% immediately after the exercise bout and recovered to initial levels 7 days later. Thirty-six known genes were upregulated after ECs compared with contralateral and isometrically stimulated muscles, including five muscle-specific genes: muscle LIM protein (MLP), muscle ankyrin repeat proteins (MARP1 and -2; also known as cardiac ankyrin repeat protein and Arpp/Ankrd2, respectively), Xin, and myosin binding protein H. The time courses of MLP and MARP expression after the injury bout (determined by quantitative real-time polymerase chain reaction) indicate that these genes are rapidly induced, reaching a peak expression level of 6–11 times contralateral values 12–24 h after the EC bout and returning to baseline within 72 h. Very little gene induction was seen after either isometric activation or passive stretch, indicating that the MLP and MARP genes may play an important and specific role in the biological response of muscle to EC-induced injury.
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Shuler, C. F., and K. R. Dalrymple. "Molecular Regulation of Tongue and Craniofacial Muscle Differentiation." Critical Reviews in Oral Biology & Medicine 12, no. 1 (January 2001): 3–17. http://dx.doi.org/10.1177/10454411010120010201.
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The molecular regulation of muscle development is tightly controlled at three distinct stages of the process: determination, differentiation, and maturation. Developmentally, specific populations of myoblasts exhibit distinct molecular phenotypes that begin to limit the ultimate characteristics of the muscle fibers. The expression of the myogenic regulatory factor family of the transcription process plays a key role in muscle development and, ultimately, in the subset of contractile genes expressed in a specific muscle. Craniofacial muscles have distinct functional requirements and associated molecular phenotypes that distinguish them from other skeletal muscles. The general principles of muscle molecular differentiation with specific reference to craniofacial muscles, such as the tongue, are discussed in this review.
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Jagla, T., F. Bellard, Y. Lutz, G. Dretzen, M. Bellard, and K. Jagla. "ladybird determines cell fate decisions during diversification of Drosophila somatic muscles." Development 125, no. 18 (September 15, 1998): 3699–708. http://dx.doi.org/10.1242/dev.125.18.3699.
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In the mesoderm of Drosophila embryos, a defined number of cells segregate as progenitors of individual body wall muscles. Progenitors and their progeny founder cells display lineage-specific expression of transcription factors but the mechanisms that regulate their unique identities are poorly understood. Here we show that the homeobox genes ladybird early and ladybird late are expressed in only one muscle progenitor and its progeny: the segmental border muscle founder cell and two precursors of adult muscles. The segregation of the ladybird-positive progenitor requires coordinate action of neurogenic genes and an interplay of inductive Hedgehog and Wingless signals from the overlying ectoderm. Unlike so far described progenitors but similar to the neuroblasts, the ladybird-positive progenitor undergoes morphologically asymmetric division. We demonstrate that the ectopic ladybird expression is sufficient to change the identity of a subset of progenitor/founder cells and to generate an altered pattern of muscle precursors. When ectopically expressed, ladybird transforms the identity of neighbouring, Kruppel-positive progenitors leading to the formation of giant segmental border muscles and supernumerary precursors of lateral adult muscles. In embryos lacking ladybird gene function, specification of two ladybird-expressing myoblast lineages is affected. The segmental border muscles do not form or have abnormal shapes and insertion sites while the number of lateral precursors of adult muscles is dramatically reduced. Altogether our results provide new insights into the genetic control of diversification of muscle precursors and indicate a further similarity between the myogenic and neurogenic pathways.
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Collins, Asiamah Amponsah, Kun Zou, Zhang Li, and Su Ying. "Mechanism and Functions of Identified miRNAs in Poultry Skeletal Muscle Development – A Review." Annals of Animal Science 19, no. 4 (October 1, 2019): 887–904. http://dx.doi.org/10.2478/aoas-2019-0049.
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AbstractDevelopment of the skeletal muscle goes through several complex processes regulated by numerous genetic factors. Although much efforts have been made to understand the mechanisms involved in increased muscle yield, little work is done about the miRNAs and candidate genes that are involved in the skeletal muscle development in poultry. Comprehensive research of candidate genes and single nucleotide related to poultry muscle growth is yet to be experimentally unraveled. However, over a few periods, studies in miRNA have disclosed that they actively participate in muscle formation, differentiation, and determination in poultry. Specifically, miR-1, miR-133, and miR-206 influence tissue development, and they are highly expressed in the skeletal muscles. Candidate genes such as CEBPB, MUSTN1, MSTN, IGF1, FOXO3, mTOR, and NFKB1, have also been identified to express in the poultry skeletal muscles development. However, further researches, analysis, and comprehensive studies should be made on the various miRNAs and gene regulatory factors that influence the skeletal muscle development in poultry. The objective of this review is to summarize recent knowledge in miRNAs and their mode of action as well as transcription and candidate genes identified to regulate poultry skeletal muscle development.
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Hain, Brian A., Stephen L. Dodd, and Andrew R. Judge. "IκBα degradation is necessary for skeletal muscle atrophy associated with contractile claudication." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 300, no. 3 (March 2011): R595—R604. http://dx.doi.org/10.1152/ajpregu.00728.2010.
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The arterial blockage in patients with peripheral arterial disease (PAD) restricts oxygen delivery to skeletal muscles distal to the blockage. In advanced-stage PAD patients, this creates a chronic ischemic condition in the affected muscles. However, in the majority of PAD patients, the muscles distal to the blockage only become ischemic during physical activity when the oxygen demands of these muscles are increased. Therefore, the skeletal muscle of most PAD patients undergoes repeated cycles of low-grade ischemia-reperfusion each time the patient is active and then rests. This has been speculated to contribute to the biochemical and morphological myopathies observed in PAD patients. The current study aimed to determine, using a rodent model, whether repeated hind limb muscle contractions during blood flow restriction to the hind limb muscles increases NF-κB activity. We, subsequently, determined whether an increase in NF-κB activity during this condition is required for the increased transcription of specific atrophy-related genes and muscle fiber atrophy. We found that hind limb muscle contractions during blood flow restriction to the limb increased NF-κB activity, the transcription of specific atrophy-related genes, and caused a 35% decrease in muscle fiber cross-sectional area. We further found that inhibition of NF-κB activity, via gene transfer of a dominant-negative inhibitor of κBα (d.n. IκBα), prevented the increase in atrophy gene expression and muscle fiber atrophy. These findings demonstrate that when blood flow to skeletal muscle is restricted, repeated cycles of muscle contraction can cause muscle fiber atrophy that requires NF-κB-IκBα signaling.
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Wong, Chao-Jen, Leo H. Wang, Seth D. Friedman, Dennis Shaw, Amy E. Campbell, Chris B. Budech, Leann M. Lewis, et al. "Longitudinal measures of RNA expression and disease activity in FSHD muscle biopsies." Human Molecular Genetics 29, no. 6 (February 21, 2020): 1030–43. http://dx.doi.org/10.1093/hmg/ddaa031.
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Abstract Advances in understanding the pathophysiology of facioscapulohumeral dystrophy (FSHD) have led to the discovery of candidate therapeutics, and it is important to identify markers of disease activity to inform clinical trial design. For drugs that inhibit DUX4 expression, measuring DUX4 or DUX4-target gene expression might be an interim measure of drug activity; however, only a subset of FHSD muscle biopsies shows evidence of DUX4 expression. Our prior study showed that MRI T2-STIR-positive muscles had a higher probability of showing DUX4 expression than muscles with normal MRI characteristics. In the current study, we performed a 1-year follow-up assessment of the same muscle with repeat MRI and muscle biopsy. There was little change in MRI characteristics over the 1-year period and, similar to the initial evaluation, MRI T2-STIR-postive muscles had a higher expression of DUX4-regulated genes, as well as genes associated with inflammation, extracellular matrix and cell cycle. Compared to the initial evaluation, overall the level of expression in these gene categories remained stable over the 1-year period; however, there was some variability for each individual muscle biopsied. The pooled data from both the initial and 1-year follow-up evaluations identified several FSHD subgroups based on gene expression, as well as a set of genes—composed of DUX4-target genes, inflammatory and immune genes and cell cycle control genes—that distinguished all of the FSHD samples from the controls. These candidate markers of disease activity need to be replicated in independent datasets and, if validated, may provide useful measures of disease progression and response to therapy.
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Hyatt, Jon-Philippe K., Roland R. Roy, Kenneth M. Baldwin, and V. Reggie Edgerton. "Nerve activity-independent regulation of skeletal muscle atrophy: role of MyoD and myogenin in satellite cells and myonuclei." American Journal of Physiology-Cell Physiology 285, no. 5 (November 2003): C1161—C1173. http://dx.doi.org/10.1152/ajpcell.00128.2003.
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Electrical activity is thought to be the primary neural stimulus regulating muscle mass, expression of myogenic regulatory factor genes, and cellular activity within skeletal muscle. However, the relative contribution of neural influences that are activity-dependent and -independent in modulating these characteristics is unclear. Comparisons of denervation (no neural influence) and spinal cord isolation (SI, neural influence with minimal activity) after 3, 14, and 28 days of treatment were used to demonstrate whether there are neural influences on muscle that are activity independent. Furthermore, the effects of these manipulations were compared for a fast ankle extensor (medial gastrocnemius) and a fast ankle flexor (tibialis anterior). The mass of both muscles plateaued at ∼60% of control 2 wk after SI, whereas both muscles progressively atrophied to <25% of initial mass at this same time point after denervation. A rapid increase in myogenin and, to a lesser extent, MyoD mRNAs and proteins was observed in denervated and SI muscles: at the later time points, these myogenic regulatory factors remained elevated in denervated, but not in SI, muscles. This widespread neural activity-independent influence on MyoD and myogenin expression was observed in myonuclei and satellite cells and was not specific for fast or slow fiber phenotypes. Mitotic activity of satellite and connective tissue cells also was consistently lower in SI than in denervated muscles. These results demonstrate a neural effect independent of electrical activity that 1) helps preserve muscle mass, 2) regulates muscle-specific genes, and 3) potentially spares the satellite cell pool in inactive muscles.
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Ravaglia, Sabrina, Alberto Malovini, Serena Cirio, Cesare Danesino, Paola De Filippi, Maurizio Moggio, Tiziana Mongini, et al. "Polymorphism in exercise genes and respiratory function in late-onset Pompe disease." Journal of Applied Physiology 131, no. 6 (December 1, 2021): 1762–71. http://dx.doi.org/10.1152/japplphysiol.00154.2020.
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Previous reports evaluated the role of exercise genes in influencing skeletal muscle phenotype and response to ERT in LOPD. Here, we investigate the role of polymorphisms in several exercise gene, focusing on respiratory muscles. ACE-DD and ACTN3-XX polymorphisms, possibly influencing muscle properties and fiber composition, were associated with more severe respiratory phenotypes.
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Kavazis, Andreas N., Ashley J. Smuder, and Scott K. Powers. "Effects of short-term endurance exercise training on acute doxorubicin-induced FoxO transcription in cardiac and skeletal muscle." Journal of Applied Physiology 117, no. 3 (August 1, 2014): 223–30. http://dx.doi.org/10.1152/japplphysiol.00210.2014.
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Doxorubicin (DOX) is a potent antitumor agent used in cancer treatment. Unfortunately, DOX can induce myopathy in both cardiac and skeletal muscle, which limits its clinical use. Importantly, exercise training has been shown to protect against DOX-mediated cardiac and skeletal muscle myopathy. However, the mechanisms responsible for this exercise-induced muscle protection remain elusive. These experiments tested the hypothesis that short-term exercise training protects against acute DOX-induced muscle toxicity, in part, due to decreased forkhead-box O (FoxO) transcription of atrophy genes. Rats ( n = 6 per group) were assigned to sedentary or endurance exercise-trained groups and paired with either placebo or DOX treatment. Gene expression and protein abundance were measured in both cardiac and skeletal muscles to determine the impact of DOX and exercise on FoxO gene targets. Our data demonstrate that DOX administration amplified FoxO1 and FoxO3 mRNA expression and increased transcription of FoxO target genes [i.e., atrogin-1/muscle atrophy F-box (MaFbx), muscle ring finger-1 (MuRF-1), and BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3)] in heart and soleus muscles. Importantly, exercise training protected against DOX-induced increases of FoxO1 and MuRF-1 in cardiac muscle and also prevented the rise of FoxO3, MuRF-1, and BNIP3 in soleus muscle. Furthermore, our results indicate that exercise increased peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) in both the heart and soleus muscles. This is important because increased PGC-1α expression is known to suppress FoxO activity resulting in reduced expression of FoxO target genes. Together, these results are consistent with the hypothesis that exercise training protects against DOX-induced myopathy in both heart (FoxO1 and MuRF-1) and skeletal muscles (FoxO3, MuRF-1, and BNIP3).
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Salem, Mohamed, P. Brett Kenney, Caird E. Rexroad, and Jianbo Yao. "Microarray gene expression analysis in atrophying rainbow trout muscle: a unique nonmammalian muscle degradation model." Physiological Genomics 28, no. 1 (December 2006): 33–45. http://dx.doi.org/10.1152/physiolgenomics.00114.2006.
Full textAbstract:
Muscle atrophy is a physiological response to diverse physiological and pathological conditions that trigger muscle deterioration through specific cellular mechanisms. Despite different signals, the biochemical changes in atrophying muscle share many common cascades. Muscle deterioration as a physiological response to the energetic demands of fish vitellogenesis represents a unique model for studying the mechanisms of muscle degradation in non-mammalian animals. A salmonid microarray, containing 16,006 cDNAs, was used to study the transcriptome response to atrophy of fast-switch muscles from gravid rainbow trout compared with sterile fish. Eighty-two unique transcripts were upregulated and 120 transcripts were downregulated in atrophying muscles. Transcripts having gene ontology identifiers were grouped according to their functions. Muscle deterioration was associated with elevated expression of genes involved in the catheptic and collagenase proteolytic pathways; the aerobic production, buffering, and utilization of ATP; and growth arrest; whereas atrophying muscle showed downregulation of genes encoding a serine proteinase inhibitor, enzymes of anaerobic respiration, muscle proteins as well as genes required for RNA and protein biosynthesis/processing. Therefore, gene transcription of the trout muscle atrophy changed in a manner similar to mammalian muscle atrophy. These changes result in an arrest of normal cell growth, protein degradation, and decreased glycolytic cellular respiration that is characteristic of the fast-switch muscle. For the first time, other changes/mechanisms unique to fish were discussed including genes associated with muscle atrophy.
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Fischer, M. Dominik, J. Rafael Gorospe, Edward Felder, Sasha Bogdanovich, F. Pedrosa-Domellöf, Rexford S. Ahima, Neal A. Rubinstein, Eric P. Hoffman, and Tejvir S. Khurana. "Expression profiling reveals metabolic and structural components of extraocular muscles." Physiological Genomics 9, no. 2 (May 10, 2002): 71–84. http://dx.doi.org/10.1152/physiolgenomics.00115.2001.
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The extraocular muscles (EOM) are anatomically and physiologically distinct from other skeletal muscles. EOM are preferentially affected in mitochondrial myopathies, but spared in Duchenne’s muscular dystrophy. The anatomical and pathophysiological properties of EOM have been attributed to their unique molecular makeup: an allotype. We used expression profiling to define molecular features of the EOM allotype. We found 346 differentially expressed genes in rat EOM compared with tibialis anterior, based on a twofold difference cutoff. Genes required for efficient, fatigue-resistant, oxidative metabolism were increased in EOM, whereas genes for glycogen metabolism were decreased. EOM also showed increased expression of genes related to structural components of EOM such as vessels, nerves, mitochondria, and neuromuscular junctions. Additionally, genes related to specialized functional roles of EOM such as the embryonic and EOM-specific myosin heavy chains and genes for muscle growth, development, and/or regeneration were increased. The EOM expression profile was validated using biochemical, structural, and molecular methods. Characterization of the EOM expression profile begins to define gene transcription patterns associated with the unique anatomical, metabolic, and pathophysiological properties of EOM.
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Loughna, P. T., S. Izumo, G. Goldspink, and B. Nadal-Ginard. "Disuse and passive stretch cause rapid alterations in expression of developmental and adult contractile protein genes in skeletal muscle." Development 109, no. 1 (May 1, 1990): 217–23. http://dx.doi.org/10.1242/dev.109.1.217.
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Contractile proteins exist as a number of isoforms that show a developmental and tissue-specific pattern of expression. Using gene-specific cDNA probes, the expression of the sarcomeric myosin heavy chain (MHC) multi-gene family and of cardiac (foetal) alpha-actin was analysed in three different rat hindlimb muscles immobilised for 5 days in either the shortened or lengthened positions. For each of the MHC genes normally expressed in adult muscle (slow, IIA and IIB), the effect of disuse alone (immobilisation in the shortened position) upon expression was markedly different to that of passive stretch (immobilisation in the lengthened position) in each of the three muscles. However, the same adult sarcomeric myosin heavy chain gene can be affected in a different, or even opposite, manner by either disuse or passive stretch depending on the muscle in which it is being expressed. The fast IIB MHC gene, for example, exhibits a rapid induction in the slow postural soleus muscle, in response to disuse but no such induction occurs in the faster plantaris and gastrocnemius muscles. Furthermore, the induction of this gene in the soleus was prevented by passive stretch. The MHC gene, normally only expressed in embryonic skeletal muscle, showed a similar response in all three muscles and was reinduced in adult muscle in response to passive stretch but not by disuse alone. In contrast, the isoform of alpha-actin which is normally only present in significant quantities in embryonic skeletal muscle and which is reduced postnatally, is not reinduced by passive stretch but is reduced still further by immobilisation in the shortened position.
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Alto, Sarah I., Chih-Ning Chang, Kevin Brown, Chrissa Kioussi, and Theresa M. Filtz. "Gene Expression Profiling of Skeletal Muscles." Genes 12, no. 11 (October 28, 2021): 1718. http://dx.doi.org/10.3390/genes12111718.
Full textAbstract:
Next-generation sequencing provides an opportunity for an in-depth biocomputational analysis to identify gene expression patterns between soleus and tibialis anterior, two well-characterized skeletal muscles, and analyze their gene expression profiling. RNA read counts were analyzed for differential gene expression using the R package edgeR. Differentially expressed genes were filtered using a false discovery rate of less than 0.05 c, a fold-change value of more than twenty, and an association with overrepresented pathways based on the Reactome pathway over-representation analysis tool. Most of the differentially expressed genes associated with soleus are coded for components of lipid metabolism and unique contractile elements. Differentially expressed genes associated with tibialis anterior encoded mostly for glucose and glycogen metabolic pathway regulatory enzymes and calcium-sensitive contractile components. These gene expression distinctions partly explain the genetic basis for skeletal muscle specialization, and they may help to explain skeletal muscle susceptibility to disease and drugs and further refine tissue engineering approaches.
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Kablar, Boris, Atsushi Asakura, Kirsten Krastel, Chuyan Ying, Linda L. May, David J. Goldhamer, and Michael A. Rudnicki. "MyoD and Myf-5 define the specification of musculature of distinct embryonic origin." Biochemistry and Cell Biology 76, no. 6 (December 1, 1998): 1079–91. http://dx.doi.org/10.1139/o98-107.
Full textAbstract:
Mounting evidence supports the notion that Myf-5 and MyoD play unique roles in the development of epaxial (originating in the dorso-medial half of the somite, e.g. back muscles) and hypaxial (originating in the ventro-lateral half of the somite, e.g. limb and body wall muscles) musculature. To further understand how Myf-5 and MyoD genes co-operate during skeletal muscle specification, we examined and compared the expression pattern of MyoD-lacZ (258/-2.5lacZ and MD6.0-lacZ) transgenes in wild-type, Myf-5, and MyoD mutant embryos. We found that the delayed onset of muscle differentiation in the branchial arches, tongue, limbs, and diaphragm of MyoD-/- embryos was a consequence of a reduced ability of myogenic precursor cells to progress through their normal developmental program and not because of a defect in migration of muscle progenitor cells into these regions. We also found that myogenic precursor cells for back, intercostal, and abdominal wall musculature in Myf-5-/-embryos failed to undergo normal translocation or differentiation. By contrast, the myogenic precursors of intercostal and abdominal wall musculature in MyoD-/- embryos underwent normal translocation but failed to undergo timely differentiation. In conclusion, these observations strongly support the hypothesis that Myf-5 plays a unique role in the development of muscles arising after translocation of epithelial dermamyotome cells along the medial edge of the somite to the subjacent myotome (e.g., back or epaxial muscle) and that MyoD plays a unique role in the development of muscles arising from migratory precursor cells (e.g., limb and branchial arch muscles, tongue, and diaphragm). In addition, the expression pattern of MyoD-lacZ transgenes in the intercostal and abdominal wall muscles of Myf-5-/- and MyoD-/- embryos suggests that appropriate development of these muscles is dependent on both genes and, therefore, these muscles have a dual embryonic origin (epaxial and hypaxial).Key words: epaxial and hypaxial muscle, Myf-5, MyoD, mouse development, somite.
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Bate, Michael, Emma Rushton, and Manfred Frasch. "A dual requirement for neurogenic genes in Drosophila myogenesis." Development 119, Supplement (December 1, 1993): 149–61. http://dx.doi.org/10.1242/dev.119.supplement.149.
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In wild-type embryos of Drosophila melanogaster, the formation of differentiated larval muscles is preceded by the segregation of small numbers of progenitor or founder cells in the embryonic mesoderm. The founder cells, characterised by the expression of genes encoding putative transcription factors such as S59 or vestigial, fuse with neighbouring myoblasts to form syncytial pre cursors of individual muscles. Founder cell segregation is deranged in embryos mutant for any of the neurogenic genes: enlarged clusters of cells expressing S59 or vestigial are detected at the sites where small numbers of founder cells segregate in the wild type. In addition, muscle differentiation is deranged in such embryos in a way that appears to be closely linked to the extent of epidermal disruption caused by the neurogenic phenotype: myoblast fusion is limited to regions of the mesoderm beneath the residual epidermis left by the hyperplasia of the nervous system, and late expression of S59 and vestigial is lost from mesoderm not lying within the margins of the residual epidermis. Thus neurogenic gene functions appear to be required both for the normal segregation of founder cells and for muscle differentiation. It is not clear whether either of these requirements reflects an essential function for any or all of the neurogenic genes within the mesoderm itself.
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Chechenova, Maria B., Sara Maes, Sandy T. Oas, Cloyce Nelson, Kaveh G. Kiani, Anton L. Bryantsev, and Richard M. Cripps. "Functional redundancy and nonredundancy between two Troponin C isoforms inDrosophilaadult muscles." Molecular Biology of the Cell 28, no. 6 (March 15, 2017): 760–70. http://dx.doi.org/10.1091/mbc.e16-07-0498.
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We investigated the functional overlap of two muscle Troponin C (TpnC) genes that are expressed in the adult fruit fly, Drosophila melanogaster: TpnC4 is predominantly expressed in the indirect flight muscles (IFMs), whereas TpnC41C is the main isoform in the tergal depressor of the trochanter muscle (TDT; jump muscle). Using CRISPR/Cas9, we created a transgenic line with a homozygous deletion of TpnC41C and compared its phenotype to a line lacking functional TpnC4. We found that the removal of either of these genes leads to expression of the other isoform in both muscle types. The switching between isoforms occurs at the transcriptional level and involves minimal enhancers located upstream of the transcription start points of each gene. Functionally, the two TpnC isoforms were not equal. Although ectopic TpnC4 in TDT muscles was able to maintain jumping ability, TpnC41C in IFMs could not effectively support flying. Simultaneous functional disruption of both TpnC genes resulted in jump-defective and flightless phenotypes of the survivors, as well as abnormal sarcomere organization. These results indicated that TpnC is required for myofibril assembly, and that there is functional specialization among TpnC isoforms in Drosophila.
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Evano, Brendan, Diljeet Gill, Irene Hernando-Herraez, Glenda Comai, Thomas M. Stubbs, Pierre-Henri Commere, Wolf Reik, and Shahragim Tajbakhsh. "Transcriptome and epigenome diversity and plasticity of muscle stem cells following transplantation." PLOS Genetics 16, no. 10 (October 30, 2020): e1009022. http://dx.doi.org/10.1371/journal.pgen.1009022.
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Adult skeletal muscles are maintained during homeostasis and regenerated upon injury by muscle stem cells (MuSCs). A heterogeneity in self-renewal, differentiation and regeneration properties has been reported for MuSCs based on their anatomical location. Although MuSCs derived from extraocular muscles (EOM) have a higher regenerative capacity than those derived from limb muscles, the molecular determinants that govern these differences remain undefined. Here we show that EOM and limb MuSCs have distinct DNA methylation signatures associated with enhancers of location-specific genes, and that the EOM transcriptome is reprogrammed following transplantation into a limb muscle environment. Notably, EOM MuSCs expressed host-site specific positional Hox codes after engraftment and self-renewal within the host muscle. However, about 10% of EOM-specific genes showed engraftment-resistant expression, pointing to cell-intrinsic molecular determinants of the higher engraftment potential of EOM MuSCs. Our results underscore the molecular diversity of distinct MuSC populations and molecularly define their plasticity in response to microenvironmental cues. These findings provide insights into strategies designed to improve the functional capacity of MuSCs in the context of regenerative medicine.
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Shum, Angie M. Y., David C. Y. Fung, Susan M. Corley, Max C. McGill, Nicholas L. Bentley, Timothy C. Tan, Marc R. Wilkins, and Patsie Polly. "Cardiac and skeletal muscles show molecularly distinct responses to cancer cachexia." Physiological Genomics 47, no. 12 (December 2015): 588–99. http://dx.doi.org/10.1152/physiolgenomics.00128.2014.
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Cancer cachexia is a systemic, paraneoplastic syndrome seen in patients with advanced cancer. There is growing interest in the altered muscle pathophysiology experienced by cachectic patients. This study reports the microarray analysis of gene expression in cardiac and skeletal muscle in the colon 26 (C26) carcinoma mouse model of cancer cachexia. A total of 268 genes were found to be differentially expressed in cardiac muscle tissue, compared with nontumor-bearing controls. This was fewer than the 1,533 genes that changed in cachectic skeletal muscle. In addition to different numbers of genes changing, different cellular functions were seen to change in each tissue. The cachectic heart showed signs of inflammation, similar to cachectic skeletal muscle, but did not show the upregulation of ubiquitin-dependent protein catabolic processes or downregulation of genes involved in cellular energetics and muscle regeneration that characterizes skeletal muscle cachexia. Quantitative PCR was used to investigate a subset of inflammatory genes in the cardiac and skeletal muscle of independent cachectic samples; this revealed that B4galt1, C1s, Serpina3n, and Vsig4 were significantly upregulated in cardiac tissue, whereas C1s and Serpina3n were significantly upregulated in skeletal tissue. Our skeletal muscle microarray results were also compared with those from three published microarray studies and found to be consistent in terms of the genes differentially expressed and the functional processes affected. Our study highlights that skeletal and cardiac muscles are affected differently in the C26 mouse model of cachexia and that therapeutic strategies cannot assume that both muscle types will show a similar response.
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Brenner, H. R., A. Herczeg, and C. R. Slater. "Synapse-specific expression of acetylcholine receptor genes and their products at original synaptic sites in rat soleus muscle fibres regenerating in the absence of innervation." Development 116, no. 1 (September 1, 1992): 41–53. http://dx.doi.org/10.1242/dev.116.1.41.
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To test the hypothesis that synaptic basal lamina can induce synapse-specific expression of acetylcholine receptor (AChR) genes, we examined the levels mRNA for the alpha- and epsilon-subunits of the AChR in regenerating rat soleus muscles up to 17 days of regeneration. Following destruction of all muscle fibres and their nuclei by exposure to venom of the Australian tiger snake, new fibres regenerated within the original basal lamina sheaths. Northern blots showed that original mRNA was lost during degeneration. Early in regeneration, both alpha- and epsilon-subunit mRNAs were present throughout the muscle fibres but in situ hybridization showed them to be concentrated primarily at original synaptic sites, even when the nerve was absent during regeneration. A similar concentration was seen in denervated regenerating muscles kept active by electrical stimulation and in muscles frozen 41–44 hours after venom injection to destroy all cells in the synaptic region of the muscle. Acetylcholine-gated ion channels with properties similar to those at normal neuromuscular junctions were concentrated at original synaptic sites on denervated stimulated muscles. Taken together, these findings provide strong evidence that factors that induce the synapse-specific expression of AChR genes are stably bound to synaptic basal lamina.
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Iyer, Shama, Christopher Ward, Joseph Stains, Alice Ryan, Eric Folker, and Richard Lovering. "Age-Dependent Changes in Nuclear Mechanotransduction as a Driver of Sarcopenia." Innovation in Aging 4, Supplement_1 (December 1, 2020): 129. http://dx.doi.org/10.1093/geroni/igaa057.424.
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Abstract Informed by evidence that dysregulated nuclear dynamics and nuclear transport may contribute to atrophy in diseased skeletal muscle, the purpose of this study was to assess nuclear deformability, permeability, transport, and mechano-signaling outputs (YAP/TAZ, a marker of mechano-responsiveness, and their downstream genes) in aging skeletal muscle. We hypothesized that aging muscle would show changes in: proteins within LINC (linker of the nucleus to the cytoskeleton) complex, lamina and nuclear pore complex (NPC), and mechano-signaling outputs, with consequent decreased nuclear deformability and increased permeability. We further expected an increase in nuclear strain would increase nuclear YAP/TAZ and downstream indicators of YAP activity (Ankrd1, Cyr61). We used young, adult and aged C57BL6 mice (~4, 14, and 26 months, respectively). Nuclei were less deformable to passive mechanical stretch ex-vivo in adult muscle fibers compared to young muscle fibers. LINC protein gene expression, YAP/TAZ protein, and expression of their downstream genes were significantly increased in adult muscles compared to young muscles. YAP/TAZ protein and their downstream genes were further increased in aged muscles, indicating hyperactivation of YAP/TAZ in aging muscle. Changes with aging in the lamina and NPC included a loss of lamin β1, Nup107 and POM 121, which could underlie the increased nuclear permeability we found in nuclei of aged muscle. In summary, these data highlight a possible role for LINC, lamina and NPC in changes of aging-related nuclear dynamics and mechano-sensing, and may represent therapeutic targets for sarcopenia. Future studies will examine how altering these components affects muscle function during aging.
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Sartorius, Carol A., Brian D. Lu, Leslie Acakpo-Satchivi, Renee P. Jacobsen, William C. Byrnes, and Leslie A. Leinwand. "Myosin Heavy Chains IIa and IId Are Functionally Distinct in the Mouse." Journal of Cell Biology 141, no. 4 (May 18, 1998): 943–53. http://dx.doi.org/10.1083/jcb.141.4.943.
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Myosin in adult murine skeletal muscle is composed primarily of three adult fast myosin heavy chain (MyHC) isoforms. These isoforms, MyHC-IIa, -IId, and -IIb, are >93% identical at the amino acid level and are broadly expressed in numerous muscles, and their genes are tightly linked. Mice with a null mutation in the MyHC-IId gene have phenotypes that include growth inhibition, muscle weakness, histological abnormalities, kyphosis (spinal curvature), and aberrant kinetics of muscle contraction and relaxation. Despite the lack of MyHC-IId, IId null mice have normal amounts of myosin in their muscles because of compensation by the MyHC-IIa gene. In each muscle examined from IId null mice, there was an increase in MyHC-IIa– containing fibers. MyHC-IIb content was unaffected in all muscles except the masseter, where its expression was extinguished in the IId null mice. Cross-sectional fiber areas, total muscle cross-sectional area, and total fiber number were affected in ways particular to each muscle. Developmental expression of adult MyHC genes remained unchanged in IId null mice. Despite this universal compensation of MyHC-IIa expression, IId null mice have severe phenotypes. We conclude that despite the similarity in sequence, MyHC-IIa and -IId have unique roles in the development and function of skeletal muscle.
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Yang, Johnson Chia-Shen, Shao-Chun Wu, Cheng-Shyuan Rau, Yi-Chun Chen, Tsu-Hsiang Lu, Yi-Chan Wu, Siou-Ling Tzeng, Chia-Jung Wu, and Ching-Hua Hsieh. "TLR4/NF-κB-Responsive MicroRNAs and Their Potential Target Genes: A Mouse Model of Skeletal Muscle Ischemia-Reperfusion Injury." BioMed Research International 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/410721.
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Background. The aim of this study was to profile TLR4/NF-κB-responsive microRNAs (miRNAs) and their potential target genes in the skeletal muscles of mice following ischemia-reperfusion injury.Methods. Thigh skeletal muscles of C57BL/6,Tlr4−/−, andNF-κB−/−mice isolated based on femoral artery perfusion were subjected to ischemia for 2 h and reperfusion for 0 h, 4 h, 1 d, and 7 d. The muscle specimens were analyzed with miRNA arrays. Immunoprecipitation with an argonaute 2- (Ago2-) specific monoclonal antibody followed by whole genome microarray was performed to identify mRNA associated with the RNA-silencing machinery. The potential targets of each upregulated miRNA were identified by combined analysis involving the bioinformatics algorithm miRanda and whole genome expression.Results. Three TLR4/NF-κB-responsive miRNAs (miR-15a, miR-744, and miR-1196) were significantly upregulated in the muscles following ischemia-reperfusion injury. The combined in silico and whole genome microarray approaches identified 5, 4, and 20 potential target genes for miR-15a, miR-744, and miR-1196, respectively. Among the 3 genes (Zbed4, Lrsam1,andDdx21) regulated by at least 2 of the 3 upregulated miRNAs,Lrsam1andDdx21are known to be associated with the innate immunity pathway.Conclusions. This study profiled TLR4/NF-κB-responsive miRNAs and their potential target genes in mouse skeletal muscle subjected to ischemia-reperfusion injury.