Academic literature on the topic 'Fibroblasts'
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Journal articles on the topic "Fibroblasts"
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Plaisancié, Pascale, Charline Buisson, Edwin Fouché, Pierre Martin, Céline Noirot, Claire Maslo, Jacques Dupuy, Françoise Guéraud, and Fabrice Pierre. "Study of the colonic epithelial-mesenchymal dialogue through establishment of two activated or not mesenchymal cell lines: Activated and resting ones differentially modulate colonocytes in co-culture." PLOS ONE 17, no. 8 (August 30, 2022): e0273858. http://dx.doi.org/10.1371/journal.pone.0273858.
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Continuous and rapid renewal of the colonic epithelium is crucial to resist the plethora of luminal deleterious agents. Subepithelial fibroblasts contribute to this turnover by regulating epithelial proliferation and differentiation. However, when intestinal homeostasis is disturbed, fibroblasts can acquire an activated phenotype and play a major role in the progression of intestinal pathologies. To evaluate the involvement of fibroblasts in the regulation of colonocytes under homeostatic or pathological conditions, we established resting and activated conditionally immortalized fibroblast cell lines (nF and mF) from mouse colonic mucosa. We then studied the epithelial-mesenchymal interactions between activated or resting fibroblasts and the normal mouse colonocytes (Co) using a co-culture model. Both fibroblastic cell lines were characterized by RT-qPCR, western blot and immunofluorescence assay. Our results showed that nF and mF cells were positive for fibroblastic markers such as vimentin and collagen 1, and negative for cytokeratin 18 and E-cadherin, attesting to their fibroblastic type. They also expressed proteins characteristic of the epithelial stem cell niche such as Grem1, CD90 or Wnt5a. Only rare nF fibroblasts were positive for α-SMA, whereas all mF fibroblasts strongly expressed this marker, supporting that mF cells were activated fibroblasts/myofibroblasts. In coculture, nF fibroblasts and Co cells strongly interacted via paracrine exchanges resulting in BMP4 production in nF fibroblasts, activation of BMP signaling in Co colonocytes, and decreased growth of colonocytes. Activated-type mF fibroblasts did not exert the same effects on Co cells, allowing colonocytes free to proliferate. In conclusion, these two colonic fibroblast lines, associated with Co cells in coculture, should allow to better understand the role of mesenchymal cells in the preservation of homeostasis and the development of intestinal pathologies.
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Caporarello, Nunzia, Jeffrey A. Meridew, Dakota L. Jones, Qi Tan, Andrew J. Haak, Kyoung M. Choi, Logan J. Manlove, Y. S. Prakash, Daniel J. Tschumperlin, and Giovanni Ligresti. "PGC1α repression in IPF fibroblasts drives a pathologic metabolic, secretory and fibrogenic state." Thorax 74, no. 8 (June 10, 2019): 749–60. http://dx.doi.org/10.1136/thoraxjnl-2019-213064.
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Idiopathic pulmonary fibrosis (IPF) is a fatal ageing-related disease linked to mitochondrial dysfunction. The present study aimed to determine whether peroxisome proliferator activated receptor gamma co-activator 1-alpha (PPARGC1A, encoding PGC1α), a master regulator of mitochondrial biogenesis, is diminished in IPF and controls pathologic fibroblast activation. Primary human IPF, control lung fibroblasts and fibroblasts sorted from bleomycin-injured mice were used to evaluate the expression and function of PGC1α. In vitro PGC1α manipulation was performed by small interfering RNA knockdown or overexpression. Fibroblast activation was assessed by quantitative PCR, Western blotting, matrix deposition, secreted cytokine array, immunofluorescence and traction force microscopy. Mitochondrial function was assessed by Seahorse analyzer and mitochondria mass and number by flow cytometry, mitochondrial DNA quantification and transmission electron microscopy (TEM). We found that PGC1α levels are stably repressed in IPF fibroblasts. After bleomycin injury in young mice, PGC1α expression drops transiently but then increases prior to fibrosis resolution. In contrast, PGC1α expression fails to recover in aged mice with persistent fibrosis. PGC1α knockdown alone in normal human lung fibroblasts reduces mitochondrial mass and function while enhancing contractile and matrix synthetic fibroblast activation, senescence-related gene expression and soluble profibrotic and prosenescence signalling. Re-expression of PGC1α in IPF fibroblasts ameliorates all of these pathological cellular functions. Pharmacological treatment of IPF fibroblasts with rosiglitazone, but not thyroid hormone, elevated PGC1α expression and attenuated fibroblast activation. The sustained repression of PGC1α and beneficial effects of its rescue in IPF fibroblasts identifies PGC1α as an important regulator of the fibroblast’s pathological state in IPF.
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Roy, Bibhas, Luezhen Yuan, Yaelim Lee, Aradhana Bharti, Aninda Mitra, and G. V. Shivashankar. "Fibroblast rejuvenation by mechanical reprogramming and redifferentiation." Proceedings of the National Academy of Sciences 117, no. 19 (April 29, 2020): 10131–41. http://dx.doi.org/10.1073/pnas.1911497117.
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Over the course of the aging process, fibroblasts lose contractility, leading to reduced connective-tissue stiffness. A promising therapeutic avenue for functional rejuvenation of connective tissue is reprogrammed fibroblast replacement, although major hurdles still remain. Toward this, we recently demonstrated that the laterally confined growth of fibroblasts on micropatterned substrates induces stem-cell-like spheroids. In this study, we embedded these partially reprogrammed spheroids in collagen-I matrices of varying densities, mimicking different three-dimensional (3D) tissue constraints. In response to such matrix constraints, these spheroids regained their fibroblastic properties and sprouted to form 3D connective-tissue networks. Interestingly, we found that these differentiated fibroblasts exhibit reduced DNA damage, enhanced cytoskeletal gene expression, and actomyosin contractility. In addition, the rejuvenated fibroblasts show increased matrix protein (fibronectin and laminin) deposition and collagen remodeling compared to the parental fibroblast tissue network. Furthermore, we show that the partially reprogrammed cells have comparatively open chromatin compaction states and may be more poised to redifferentiate into contractile fibroblasts in 3D-collagen matrix. Collectively, our results highlight efficient fibroblast rejuvenation through laterally confined reprogramming, which has important implications in regenerative medicine.
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McDonald, Lindsay T., Meenal Mehrotra, and Amanda C. LaRue. "Hematopoietic Origin of Murine Lung Fibroblasts." Stem Cells International 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/159713.
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Multiple origins, including the bone marrow, have been suggested to contribute to fibroblast populations in the lung. Using bone marrow reconstitution strategies, the present study tested the hypothesis that the bone marrow hematopoietic stem cell (HSC) gives rise to lung tissue fibroblastsin vivo. Data demonstrate that the nonadherent bone marrow fraction is enriched for CD45+HSC-derived cells and was able to reconstitute hematopoiesis in lethally irradiated animals. Analysis of peripheral blood and lung tissues from engrafted mice demonstrated the ability of this population to give rise to CD45+/Discoidin-Domain Receptor-2+(DDR2) circulating fibroblast precursors (CFPs) in blood and fibroblast populations in lung. An HSC origin for lung fibroblasts was confirmed using a novel clonal cell transplantation method in which the bone marrow is reconstituted by a clonal population derived from a single HSC. Together, these findings provide evidence for an HSC contribution to lung fibroblasts and demonstrate a circulating intermediate through the CD45+/DDR2+HSC-derived CFP.
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Strutz, F., H. Okada, C. W. Lo, T. Danoff, R. L. Carone, J. E. Tomaszewski, and E. G. Neilson. "Identification and characterization of a fibroblast marker: FSP1." Journal of Cell Biology 130, no. 2 (July 15, 1995): 393–405. http://dx.doi.org/10.1083/jcb.130.2.393.
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We performed subtractive and differential hybridization for transcript comparison between murine fibroblasts and isogenic epithelium, and observed only a few novel intracellular genes which were relatively specific for fibroblasts. One such gene encodes a filament-associated, calcium-binding protein, fibroblast-specific protein 1 (FSP1). The promoter/enhancer region driving this gene is active in fibroblasts but not in epithelium, mesangial cells or embryonic endoderm. During development, FSP1 is first detected by in situ hybridization after day 8.5 as a postgastrulation event, and is associated with cells of mesenchymal origin or of fibroblastic phenotype. Polyclonal antiserum raised to recombinant FSP1 protein stained the cytoplasm of fibroblasts, but not epithelium. Only occasional cells stain with specific anti-FSP1 antibodies in normal parenchymal tissue. However, in kidneys fibrosing from persistent inflammation, many fibroblasts could be identified in interstitial sites of collagen deposition and also in tubular epithelium adjacent to the inflammatory process. This pattern of anti-FSP1 staining during tissue fibrosis suggests, as a hypothesis, that fibroblasts in some cases arise, as needed, from the local conversion of epithelium. Consistent with this notion that FSP1 may be involved in the transition from epithelium to fibroblasts are experiments in which the in vitro overexpression of FSP1 cDNA in tubular epithelium is accompanied by conversion to a mesenchymal phenotype, as characterized by a more stellate and elongated fibroblast-like appearance, a reduction in cytokeratin, and new expression of vimentin. Similarly, tubular epithelium submerged in type I collagen gels exhibited the conversion to a fibroblast phenotype which includes de novo expression of FSP1 and vimentin. Use of the FSP1 marker, therefore, should further facilitate both the in vivo studies of fibrogenesis and the mapping of cell fate among fibroblasts.
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Lauritano, Dorina, Alberta Lucchese, Dario Di Stasio, Fedora Della Vella, Francesca Cura, Annalisa Palmieri, and Francesco Carinci. "Molecular Aspects of Drug-Induced Gingival Overgrowth: An In Vitro Study on Amlodipine and Gingival Fibroblasts." International Journal of Molecular Sciences 20, no. 8 (April 25, 2019): 2047. http://dx.doi.org/10.3390/ijms20082047.
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Gingival overgrowth is a serious side effect that accompanies the use of amlodipine. Several conflicting theories have been proposed to explain the fibroblast’s function in gingival overgrowth. To determine whether amlodipine alters the fibrotic response, we investigated its effects on treated gingival fibroblast gene expression as compared with untreated cells. Materials and Methods: Fibroblasts from ATCC® Cell Lines were incubated with amlodipine. The gene expression levels of 12 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway was investigated in treated fibroblasts cell culture, as compared with untreated cells, by real time PCR. Results: Most of the significant genes were up-regulated. (CTNND2, COL4A1, ITGA2, ITGA7, MMP10, MMP11, MMP12, MMP26) except for COL7A1, LAMB1, MMP8, and MMP16, which were down-regulated. Conclusion: These results seem to demonstrate that amlodipine has an effect on the extracellular matrix of gingival fibroblast. In the future, it would be interesting to understand the possible effect of the drug on fibroblasts of patients with amlodipine-induced gingival hyperplasia.
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Osorio, José Henry. "Producción de metabolitos en fibroblastos incubados con acido oleico deuterado./Metabolite production of fibroblasts incubated with deuterated oleic acid." Archivos de Medicina (Manizales) 13, no. 2 (December 15, 2013): 202–7. http://dx.doi.org/10.30554/archmed.13.2.24.2013.
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Objetivo: los estudios in vitro, que buscan intermediarios de la degradación mitocondrial de ácidos grasos, facilitan el diagnóstico de alteraciones hereditarias o adquiridas en esa ruta metabólica, el presente estudio analiza la produccion de metabolitos en fibroblastos incubados con acido oleico deuterado. Materiales y métodos: fibroblastos de personas sin antecedentes de alteraciones metabólicas, fueron incubados en presencia de ácido oléico deuterado, y sus metabolitos fueron analizados mediante cromatografía de gases acoplada a espectrometría de masas (GC-MS) Resultados: Se encontró un perfil característico luego de la incubación de este sustrato por fibroblastos. Conclusiones: Este sustrato podría ser usado para realizar estudios in vitro de algunas deficiencias de la β-oxidació mitocondrial de ácidos grasos, mediante la comparación de fibroblastos normales vs fibroblastos de pacientes que presenten deficiciencias de esa vía metabólica. Objective: In vitro studies for searching intermediates of mitochondrial fatty acid degradation,are a tool for diagnosis of hereditary or adquired alterations of the above mentionedmetabolic pathway. The present work analizes the metabolite production in fibroblastsincubated with deuterated oleic acid. Materials and methods: fibroblasts of personswithout antecedents of metabolic alterations, were incubated with deuterated oleic acidand its metabolites were analyzed using gas chromatograpy-mass spectrometry (GCMS).Results. It was found a characteristic profile after incubation of fibroblats with thissubstrate. Conclusion: this substrate could be used to perform in vitro studies of somemitochondrial fatty acid β-oxidación deficiencies, by comparison of normal fibroblastsvs fibroblats of patients who present defiencies of the above named metabolic pathway
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Kurniawati, Yuli, Sudigdo Adi, Achadiyani Achadiyani, Oki Suwarsa, Dimas Erlangga, and Tenny Putri. "KULTUR PRIMER FIBROBLAS: PENELITIAN PENDAHULUAN." Majalah Kedokteran Andalas 38, no. 1 (May 28, 2015): 33. http://dx.doi.org/10.22338/mka.v38.i1.p33-40.2015.
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AbstrakKultur sel fibroblas banyak digunakan untuk penelitian proses penyembuhan luka dan penuaankulit. Metode ini digunakan untuk melihat perkembangan sel, proliferasi kinetik seluler, sertabiosintesis komponen matriks ekstraseluler. Penelitian pendahuluan ini dilakukan untuk optimasiteknik laboratorium serta berbagai kendala yang didapatkan saat kultur fibroblas. Kultur primerfibroblas dibagi menjadi 2 jenis sampel yaitu sampel yang berasal dari embrio mencit usia 7,5–9,5 hari, dan kulit pasien keloid. Sampel dari embrio mencit dilakukan kultur primer denganmetode dissociated fibroblast. Sampel jaringan keloid dan kulit normal dikultur dengan metodeskin explant. Fibroblas yang berasal dari kultur primer embrio mencit tumbuh baik sehinggadapat dilakukan subkultur dan disimpan di dalam nitrogen cair suhu -198°C. Fibroblas yangberasal dari sampel keloid pertama tumbuh sesuai pola pertumbuhan fibroblas, namun padasampel kedua terdapat kontaminasi Paecilomyces sp. yang merupakan salah satu jenis jamurkontaminan. Sel fibroblas mudah untuk dikultur karena memiliki kemampuan tumbuh danmelekat yang tinggi serta regenerasi cepat, namun penelitian lebih lanjut untuk optimasi teknikkultur dan pencegahan kontaminasi masih dibutuhkan sehingga sel dapat tumbuh baik.AbstractFibroblast cell culture method has been used for wound healing and skin aging studies. Thismethod was used for cell development imaging study, celullar kinetic proliferation andextracelullar matrix component biosynthesis. This preeliminary study was done for laboratoricaltechnic optimation as well as problems appeared in fibroblast culture. Fibroblasts primary culturewas divided into 2 type of samples, from 7.5-9.5-day-mice embryo and keloid-patient skin.Primary culture with dissociated fibroblast method was done for mice embryo sample. Keloidtissue sample and normal skin were cultured with skin explant method. Fibroblasts that weretaken from mice embryo primary culture grew well therefore subculture can be done and kept in -198°C liquid nitrogen storage. Fibroblasts that were taken from first keloid sample grewaccording to fibroblast growth pattern, but, there was contamination with Paecilomyces sp. whichwas one of the contaminating fungi. Fibroblast cells are easy to be cultured as they have growthability and high adhesion capability as well as rapid regeneration, but, further study for culturedtechnical optimation and contamination prevention are still neededthereforethe cells can growwell.
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Cai, Zhou, Hua Guo, Jing Qian, Wei Liu, Yuanyuan Li, Liang Yuan, You Zhou, et al. "Effects of bone morphogenetic protein 4 on TGF-β1-induced cell proliferation, apoptosis, activation and differentiation in mouse lung fibroblasts via ERK/p38 MAPK signaling pathway." PeerJ 10 (July 27, 2022): e13775. http://dx.doi.org/10.7717/peerj.13775.
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Fibroblasts, in particular myofibroblasts, are the critical effector cells in idiopathic pulmonary fibrosis (IPF), a deadly lung disease characterized by abnormal lung remodeling and the formation of “fibroblastic foci”. Aberrant activation of TGF-β1 is frequently encountered and promotes fibroblast proliferation, activation, and differentiation in pulmonary fibrosis. Hence, the inhibition of TGF-β1-induced lung fibroblast activation holds promise as a therapeutic strategy for IPF. The present study aimed to investigate the potential effect and underlying mechanisms of bone morphogenetic protein 4 (BMP4) on TGF-β1-induced proliferation, apoptosis, activation and myofibroblast differentiation of adult lung fibroblasts. Here, we demonstrated that BMP4 expression was significantly decreased in TGF-β1-stimulated mouse primary lung fibroblasts (PLFs). BMP4 inhibited proliferation and apoptosis resistance of TGF-β1-stimulated mouse PLFs. BMP4 suppressed TGF-β1-induced fibroblast activation and differentiation in mouse PLFs. We also found that BMP4 inhibited TGF-β1-induced ERK and p38 MAPK phosphorylation. Our findings indicate that BMP4 exerts its anti-fibrotic effects by regulating fibroblast proliferation, apoptosis, activation and differentiation via the inhibition of the ERK/p38 MAPK signaling pathway, and thus has a potential for the treatment of pulmonary fibrosis.
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Jara, Paul, Jazmin Calyeca, Yair Romero, Luis Plácido, Guoying Yu, Naftali Kaminski, Vilma Maldonado, José Cisneros, Moisés Selman, and Annie Pardo. "Matrix metalloproteinase (MMP)-19-deficient fibroblasts display a profibrotic phenotype." American Journal of Physiology-Lung Cellular and Molecular Physiology 308, no. 6 (March 15, 2015): L511—L522. http://dx.doi.org/10.1152/ajplung.00043.2014.
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Idiopathic pulmonary fibrosis (IPF) is a progressive and usually lethal interstitial lung disease of unknown etiology characterized by aberrant activation of epithelial cells that induce the migration, proliferation and activation of fibroblasts. The resulting distinctive fibroblastic/myofibroblastic foci are responsible for the excessive extracellular matrix (ECM) production and abnormal lung remodeling. We have recently found that matrix metalloproteinase 19 (MMP-19)-deficient ( Mmp19−/−) mice develop an exaggerated bleomycin-induced lung fibrosis, but the mechanisms are unclear. In this study, we explored the effect of MMP-19 deficiency on fibroblast gene expression and cell behavior. Microarray analysis of Mmp19−/− lung fibroblasts revealed the dysregulation of several profibrotic pathways, including ECM formation, migration, proliferation, and autophagy. Functional studies confirmed these findings. Compared with wild-type mice, Mmp19−/− lung fibroblasts showed increased α1 (I) collagen gene and collagen protein production at baseline and after transforming growth factor-β treatment and increased smooth muscle-α actin expression ( P < 0.05). Likewise, Mmp19-deficient lung fibroblasts showed a significant increase in proliferation ( P < 0.01) and in transmigration and locomotion over Boyden chambers coated with type I collagen or with Matrigel ( P < 0.05). These findings suggest that, in lung fibroblasts, MMP-19 has strong regulatory effects on the synthesis of key ECM components, on fibroblast to myofibroblast differentiation, and in migration and proliferation.
Dissertations / Theses on the topic "Fibroblasts"
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Sipert, Carla Renata. "Produção de MIP-1alfa e SDF-1 por fibroblastos de polpa dental humana em cultura frente ao desafio com Enterococcus faecalis inativado por calor." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/25/25138/tde-15102008-164844/.
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A polpa dental é formada de tecido conjuntivo frouxo sendo constituída por diversas células, dentre as quais os fibroblastos são as mais numerosas. Ao serem submetidas a agressões diversas, estas células respondem com a liberação de substâncias, tais como citocinas e quimiocinas, que participam de maneira ativa no processo inflamatório. Assim sendo, este trabalho teve como proposição: 1. avaliar a capacidade de fibroblastos de polpa dental humana em cultura em produzirem as quimiocinas MIP-l\'alfa\' /CCL3 e SDF-1/CXCL12; 2. avaliar a produção destas quimiocinas pelos fibroblastos quando estimulados por Enterococcus faecalis morto por calor com relação à quantidade de bactérias por célula e 3. avaliar a liberação destas quimiocinas com relação ao tempo de estímulo. Para o estabelecimento das culturas, foi coletada a polpa de terceiro molar hígido de um paciente saudável. O tecido foi extraído, armazenado e picotado em meio de cultura para fibroblastos (DMEM), os quais foram utilizados a partir da quarta passagem. Após adesão das células a placas de 24 poços, o meio de cultura contendo Enterococcus .faecalis morto por calor numa concentração correspondente a 1, 10 e 100 bactérias por fibroblasto foi adicionado aos poços. Após 1, 6 e 24 horas, o sobrenadante das células foi coletado para a análise por ELISA. A análise estatística foi realizada aplicando-se o teste Kruskal-Wallis com nível de significância de 5%. A produção de MIP-l\'alfa\' /CCL3 e SDF-l/CXCL12 pelas células pôde ser detectada por ELISA. Os fibroblastos pulpares se mostraram capazes de produzir SDF-1 constitutivamente sendo que o estímulo bacteriano levou a uma diminuição estatisticamente significativa desta produção. A produção de MIP-l\'alfa\' também foi detectada tanto de maneira constitutiva como em resposta ao desafio microbiano. Enquanto a concentração intermediária de bactéria por fibroblasto (10:1) mostrou uma produção semelhante ao grupo controle, as concentrações de 1 e 100 bactérias por fibroblasto induziram aumento maior na primeira hora de estímulo. Essas diferenças, entretanto, não foram estatisticamente significativas. A capacidade dos fibroblastos secretarem quimiocinas, como MIP-l\'alfa\' e SDF-1, reforça a importância dessas células dentro do contexto de imunidade e inflamação pulpar, principalmente por serem as células mais numerosas deste microambiente.Dental pulp is a connective tissue structure constituted by many different cell types. Among them, the fibroblasts are the most frequent ones. When challenged by different aggressive agents, these cells are able to release some substances like cytokines and chemokines, which are essential to trigger the inflammatory process. The aims of this study were: 1. to evaluate the ability of fibroblasts to produce the chemokines MIP-l\'alfa\'/CCL3) and SDF-1/CXCL12; 2. to evaluate the expression of these chemokines by fibroblasts when challenged by heat killed Enterococcus. faecalis in gradual concentrations and 3. to evaluate the production of these chemokines in a time course manner. The dental pulp from non-carious third molar was collected from a healthy patient. Explants were made and stocked in culture medium (DMEM) for fibroblasts growth. The cells were used since passage four. In a 24-well plate and after reaching confluence, culture medium alone or containing heat killed E. faecalis at proportion 1:1, 10:1 and 100:1 bacteria:fibroblast, were added to the fibroblasts. After 1, 6 and 24 hours, the supernatants were collected for analysis. The protein detection of MIP-l\'alfa\'/CCL3 and SDF-1/CXCL12 was performed by ELISA. For statistical analysis, data were assessed by Kruskal-Wallis followed by Miller post-test. Significance levels of 5% were adopted. Production of both chemokines was detected by ELISA. Pulp fibroblasts were able to produce SDF-1 constitutively. This production decreased with the increase in the number of heat killed E. faecalis increased (p < 0.05). Production of MIP-l\'alfa\' was detected in unchallenged and challenged cells. The median bacterial concentration (10:1) presented a profile production similar to that of unstimulated cells. Bacterial concentrations of 1 and 100 microrganisms/cell showed a highly enhanced production of MIP-l\'alfa\' at the first hour of stimulum; however, these data were not statistically significant (p > 0.05). Fibroblasts ability to produce chemokines, like MIP-l\'alfa\' and SDF-1, confirms their importance at immune and inflammatory events in dental pulp, specially being fibroblasts the most abundant cells at this microenvironment .
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Kashpur, Olga. "Oxygen-mediated basic fibroblast growth factor (FGF2) effects on adult human dermal fibroblasts." Digital WPI, 2015. https://digitalcommons.wpi.edu/etd-dissertations/546.
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This thesis investigates the effects of low oxygen culture conditions and fibroblast growth factor-2 (FGF2) on adult human dermal fibroblasts.
It was previously shown that low oxygen and FGF2 culture conditions lead to an extension of proliferative lifespan, low-level activation of stem cell genes, and global transcriptional changes in adult human dermal fibroblasts. Additionally, an increased in vivo tissue regenerative response can be observed when human muscle-derived fibroblasts grown with FGF2 and low oxygen are implanted into mouse muscle injury, leading to a decrease in collagen deposition and scar formation and increase of functional skeletal muscle regeneration, including formation of Pax7+ muscle stem cells.
These findings led to an analysis of key cellular oxygen sensors, hypoxia inducible factors (HIFs) and their role in this regenerative response. Directly linking these factors with the regenerative response, I have shown, with knockdown experiments, that HIF-2α is required for the increased proliferative capability and decreased senescence of human dermal fibroblasts (hDFs) induced by hypoxia. I have also determined that low oxygen causes an early and transient increase of HIF-1α and late and sustained increase of HIF-2α protein accompanied by increased nuclear translocation. Using overexpression and knockdown approaches via lent-virus, I determined that HIF-2α appears to modulate FGF2 signaling through the FGF receptors. First, under low oxygen conditions, exogenous FGF2 led to downregulation of endogenous FGF2, which can be mimicked by overexpression of HIF-2α. In ambient oxygen we didn't see this effect. Second, HIF-2α overexpression appears to lead to increases in FGFR1 phosphorylation and consequently increased ERK1/2 phosphorylation, and increases in the expression of heparan sulfate modifying enzymes (NDST1, NDST2, and EXTL2). Lastly, sustained supplementation with FGF2 in low oxygen inhibits receptor-mediated FGF2 signaling.
To understand these effects at the transcriptional level, using microarray technology, we identified oxygen-mediated FGF2 effects on genes involved in cell survival and proliferation.
Through bioinformatics analyses, I determined that genes involved in wound healing (extracellular matrix genes, adhesion molecules, cytokines) are upregulated in FGF2 treated fibroblasts grown under low oxygen. By utilizing a gain-of-function approach, we were able to assess the effects of altered HIF-2α activity on the expression of Oct4, Sox2, Nanog, Rex1, and Lin28 in adult hDFs. The results indicate that overexpression of the HIF-2α transcription factor increases Oct4 mRNA, but not Oct4 protein, levels, and had no effect on Nanog and Lin28 proteins. HIF-2α overexpression also mediated FGF2 induction of Sox2 and Rex1 proteins of higher molecular weight.
This thesis expands our knowledge about effects of low oxygen and FGF2 on adult human dermal fibroblasts and explains in part, how FGF2 under low oxygen conditions may lead to increased proliferation, extended life span, regenerative competency and increased developmental plasticity of adult hDFs.
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Grandi, Fabrizio [UNESP]. "Fibroblastos associados ao câncer e correlação com parãmetros patológicos em melanomas cutâneos caninos." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/95886.
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O melanoma é uma das neoplasias cutâneas mais comumente diagnosticadas no homem e nos cães. O microambiente tumoral é composto pelas células neoplásicas e células estromais interagindo constantemente para garantir a progressão tumoral. Os fibroblastos associados ao câncer (FAC) representam uma população heterogênea de células caracterizadas pela expressão de diversos marcadores incluindo a proteína α-SMA e S100A4. Acredita-se que estas células originem-se de diversas fontes incluindo a transição endotelial fibroblástica. Neste trabalho, quantificamos a imunoexpressão da prpteína S100A4 nos fibroblastos associados ao câncer em melanomas cutâneos caninos, verificamos a potencial contribuição das células endoteliais na gênese desta população e correlacionamos os achados com parâmetros patológicos, incluindo a microdensidade vascular. Quarenta e oito casos de melanoma dermais caninos (21 epitelióides, 14 fusiformes e 13 mistos) previamente categorizados nos níveis de Clark 4, 5 e até 4 foram submetidos a imunofluorescência dupla utilizando os anticorpos primários α-SMA, fator de Von Willebrand (vWF) e S100A4 objetivando-se caracterizar os fibroblastos associados ao câncer e a contribuição da transição endotelial mesenquimal. Os melanomas não pigmentados foram caracterizados pela imunoistoquímica utilizando-se os anticorpos vimentina, pancitoqueratina, S100 e Melan A. A densidade microvascular foi analisada utilizando-se a técnica de imunofluorescência e o anticorpo primário anti-fator de Von Willebrand. O cálculo do número de vasos foi realizado selecionando-se cinco campos microscópicos de 200x contendo o maior número de vasos. O percentul de expressão da proteína S100A4 foi calculado através da técnica de segmentação de conglomerados de cor. Apenas um caso demonstrou...
Skin melanoma is one of the most common skin neoplasm seen in humans and dogs. Tumor microenvironment is composed by cancer cells and stromal cells that interacts to guarantee tumor progression. Cancer associated fibroblasts (CAF) represents a heterogeneous cell population characterized by expression of several markers including α-SMA and S100A4 proteins. These cells are thought to derive from different sources including endothelial-to-fibroblast transition. Here we characterize CAF in canine skin melanomas, verify the potential contribution of the endothelial cells to this population and correlate findings to pathological parameters, including microvascular density (MVD). Forth-eight cases of canine dermal melanomas (21 epithelioid, 14 spindle and 13 mixed) classified under Clark´s level 4 and 5 were submitted to a double immunofluorescence assay using primary antibodies α-SMA, Von Willebrand Factor (vWF) and S100A4 in order to characterize cancer associated fibroblasts and verify the contribution of endothelial to fibroblast transition. Non-pigmented samples were characterized by immunohistochemistry using primary antibodies pan-cytokeratin, vimentin, S100 and Melan A. Microvascular density was evaluated by immunofluorescent assay using vWF and by calculating total number of vessels in five 200x fields (“hotspots”).S100A4 imunoexpression was calculated using K-means clustering segmentation method. Only one case showed α-SMA and vWF co-expression restricted to myofibroblasts in tumor stroma. The cells were predominantly peritumoral and periadnexal. S100A4 expression was significantly different among three histotypes with mixed melanomas displaying lesser percentage of positive cells. Some neoplastic cells mainly in spindle cell melanomas were also positive for S100A4. There were no significant differences between MVD/histotypes... (Complete abstract click electronic access below)
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Silva, Rubia Bueno da [UNESP]. "Efeitos dos fatores de crescimento fibroblástico 10 e 18 (FGFs 10 e 18) sobre a esteroidogênese em ovários fetais bovinos." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/105894.
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Durante o desenvolvimento ovariano fetal, a formação folicular inicial é decisiva para a fertilidade da fêmea, pois define sua reserva gametogênica. Tem sido proposto que a progesterona e o estradiol desempenham papel regulatório na foliculogênese pré-antral, de forma que sua produção reduzida em ovários fetais bovinos antecede o surgimento de folículos primordiais e primários. Recentemente, os FGFs 10 e 18 foram reportados em folículos ovarianos bovinos como redutores dos níveis de esteróides, o que parece envolver a inibição da expressão de enzimas necessárias à esteroidogênese. Em adição, a expressão do FGF10 foi observada durante o desenvolvimento ovariano fetal bovino, e esteve positivamente associada ao aumento no número de folículos primários. O presente estudo investigou primeiramente o padrão de expressão do RNAm das enzimas esteroidogênicas (StAR, CYP11A1, 3β-HSD, CYP17A1, CYP19A1 e 17β-HSD) em ovários de fetos bovinos em idades gestacionais específicas (60, 75, 90, 120, 150 e 210 dias). Todos os genes investigados se mostraram expressos e regulados ao longo da gestação. Os níveis de RNAm da CYP19A1 diminuíram dos 60 para os 90 dias, sugerindo envolvimento desta enzima com a produção decrescente de estradiol observada previamente durante este período gestacional. A expressão das demais enzimas foi elevada ao longo da gestação, coincidente com o aumento da competência esteroidogênica descrito preliminarmente durante o desenvolvimento folicular inicial. Em adição, foi investigada a participação dos FGFs 10 e 18 na esteroidogênese ovariana fetal bovina. A expressão do FGF18 e de seus receptores (FGFR2C, FGFR3C e FGFR4) foi detectada em ovários fetais bovinos ao longo da gestação (60, 75, 90, 120, 150 e 210 dias). A abundância de RNAm do FGF18 aumentou...
During fetal ovarian development, early follicular formation is essential to female fertility, when the gametogenic reserve is defined. It has been proposed that progesterone and estradiol play regulatory role on preantral folliculogenesis, once its reduced production in bovine fetal ovaries precedes primordial and primary follicle assembly. Recentlly, FGFs 10 and 18 were reported in bovine ovarian follicles as reducers of steroids levels, and this seems to involve the inhibition of enzymes necessary to steroidogenesis. In addition, FGF10 expression was observed during bovine fetal ovary development, and it was positively associated with the elevation on primary follicles number. The present study first investigated the mRNA expression patterns for steroidogenic enzymes (StAR, CYP11A1, HSD3B1, CYP17A1, CYP19A1 and HSD17B1) in bovine fetal ovaries at specific gestational ages (60, 75, 90, 120, 150 e 210 days). Expression of all investigated genes was detected and regulated through gestation. Messenger RNA levels of CYP19A1 decreased from days 60 to 90 of gestation, suggesting involvement of this enzyme on decrescent estradiol production previously observed during this gestational period. The expression of other enzymes was elevated during gestational period, which was coincident with the enhance of steroidogenic competence previously described during early follicular development. In addition, the participation of FGFs 10 and 18 on steroidogenesis in bovine fetal ovaries was investigated. The expression of FGF18 and its receptors (FGFR2C, FGFR3C and FGFR4) was detected in bovine fetal ovaries through gestation (60, 75, 90, 120, 150 e 210 days). The mRNA abundance of FGF18 enhanced between 90 and 120 days and decreased at 210 days. The expression of FGFR2C and FGFR4 did not vary during... (Complete abstract click electronic access below)
5
Silva, Rubia Bueno da. "Efeitos dos fatores de crescimento fibroblástico 10 e 18 (FGFs 10 e 18) sobre a esteroidogênese em ovários fetais bovinos /." Botucatu, 2012. http://hdl.handle.net/11449/105894.
Full textAbstract:
Orientador: José Buratini JuniorBanca: José Antonio Visitin
Banca: Guilherme de Paula Nogueira
Banca: Fernanda da Cruz Landim e Alvarenga
Banca: Sony Dimas Bicudo
Resumo: Durante o desenvolvimento ovariano fetal, a formação folicular inicial é decisiva para a fertilidade da fêmea, pois define sua reserva gametogênica. Tem sido proposto que a progesterona e o estradiol desempenham papel regulatório na foliculogênese pré-antral, de forma que sua produção reduzida em ovários fetais bovinos antecede o surgimento de folículos primordiais e primários. Recentemente, os FGFs 10 e 18 foram reportados em folículos ovarianos bovinos como redutores dos níveis de esteróides, o que parece envolver a inibição da expressão de enzimas necessárias à esteroidogênese. Em adição, a expressão do FGF10 foi observada durante o desenvolvimento ovariano fetal bovino, e esteve positivamente associada ao aumento no número de folículos primários. O presente estudo investigou primeiramente o padrão de expressão do RNAm das enzimas esteroidogênicas (StAR, CYP11A1, 3β-HSD, CYP17A1, CYP19A1 e 17β-HSD) em ovários de fetos bovinos em idades gestacionais específicas (60, 75, 90, 120, 150 e 210 dias). Todos os genes investigados se mostraram expressos e regulados ao longo da gestação. Os níveis de RNAm da CYP19A1 diminuíram dos 60 para os 90 dias, sugerindo envolvimento desta enzima com a produção decrescente de estradiol observada previamente durante este período gestacional. A expressão das demais enzimas foi elevada ao longo da gestação, coincidente com o aumento da competência esteroidogênica descrito preliminarmente durante o desenvolvimento folicular inicial. Em adição, foi investigada a participação dos FGFs 10 e 18 na esteroidogênese ovariana fetal bovina. A expressão do FGF18 e de seus receptores (FGFR2C, FGFR3C e FGFR4) foi detectada em ovários fetais bovinos ao longo da gestação (60, 75, 90, 120, 150 e 210 dias). A abundância de RNAm do FGF18 aumentou... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: During fetal ovarian development, early follicular formation is essential to female fertility, when the gametogenic reserve is defined. It has been proposed that progesterone and estradiol play regulatory role on preantral folliculogenesis, once its reduced production in bovine fetal ovaries precedes primordial and primary follicle assembly. Recentlly, FGFs 10 and 18 were reported in bovine ovarian follicles as reducers of steroids levels, and this seems to involve the inhibition of enzymes necessary to steroidogenesis. In addition, FGF10 expression was observed during bovine fetal ovary development, and it was positively associated with the elevation on primary follicles number. The present study first investigated the mRNA expression patterns for steroidogenic enzymes (StAR, CYP11A1, HSD3B1, CYP17A1, CYP19A1 and HSD17B1) in bovine fetal ovaries at specific gestational ages (60, 75, 90, 120, 150 e 210 days). Expression of all investigated genes was detected and regulated through gestation. Messenger RNA levels of CYP19A1 decreased from days 60 to 90 of gestation, suggesting involvement of this enzyme on decrescent estradiol production previously observed during this gestational period. The expression of other enzymes was elevated during gestational period, which was coincident with the enhance of steroidogenic competence previously described during early follicular development. In addition, the participation of FGFs 10 and 18 on steroidogenesis in bovine fetal ovaries was investigated. The expression of FGF18 and its receptors (FGFR2C, FGFR3C and FGFR4) was detected in bovine fetal ovaries through gestation (60, 75, 90, 120, 150 e 210 days). The mRNA abundance of FGF18 enhanced between 90 and 120 days and decreased at 210 days. The expression of FGFR2C and FGFR4 did not vary during... (Complete abstract click electronic access below)
Doutor
6
Grandi, Fabrizio. "Fibroblastos associados ao câncer e correlação com parãmetros patológicos em melanomas cutâneos caninos /." Botucatu, 2012. http://hdl.handle.net/11449/95886.
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Orientador: Noeme Sousa RochaBanca: Hélio Amante Miot
Banca: Bruno Cogliati
Resumo: O melanoma é uma das neoplasias cutâneas mais comumente diagnosticadas no homem e nos cães. O microambiente tumoral é composto pelas células neoplásicas e células estromais interagindo constantemente para garantir a progressão tumoral. Os fibroblastos associados ao câncer (FAC) representam uma população heterogênea de células caracterizadas pela expressão de diversos marcadores incluindo a proteína α-SMA e S100A4. Acredita-se que estas células originem-se de diversas fontes incluindo a transição endotelial fibroblástica. Neste trabalho, quantificamos a imunoexpressão da prpteína S100A4 nos fibroblastos associados ao câncer em melanomas cutâneos caninos, verificamos a potencial contribuição das células endoteliais na gênese desta população e correlacionamos os achados com parâmetros patológicos, incluindo a microdensidade vascular. Quarenta e oito casos de melanoma dermais caninos (21 epitelióides, 14 fusiformes e 13 mistos) previamente categorizados nos níveis de Clark 4, 5 e até 4 foram submetidos a imunofluorescência dupla utilizando os anticorpos primários α-SMA, fator de Von Willebrand (vWF) e S100A4 objetivando-se caracterizar os fibroblastos associados ao câncer e a contribuição da transição endotelial mesenquimal. Os melanomas não pigmentados foram caracterizados pela imunoistoquímica utilizando-se os anticorpos vimentina, pancitoqueratina, S100 e Melan A. A densidade microvascular foi analisada utilizando-se a técnica de imunofluorescência e o anticorpo primário anti-fator de Von Willebrand. O cálculo do número de vasos foi realizado selecionando-se cinco campos microscópicos de 200x contendo o maior número de vasos. O percentul de expressão da proteína S100A4 foi calculado através da técnica de segmentação de conglomerados de cor. Apenas um caso demonstrou... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Skin melanoma is one of the most common skin neoplasm seen in humans and dogs. Tumor microenvironment is composed by cancer cells and stromal cells that interacts to guarantee tumor progression. Cancer associated fibroblasts (CAF) represents a heterogeneous cell population characterized by expression of several markers including α-SMA and S100A4 proteins. These cells are thought to derive from different sources including endothelial-to-fibroblast transition. Here we characterize CAF in canine skin melanomas, verify the potential contribution of the endothelial cells to this population and correlate findings to pathological parameters, including microvascular density (MVD). Forth-eight cases of canine dermal melanomas (21 epithelioid, 14 spindle and 13 mixed) classified under Clark's level 4 and 5 were submitted to a double immunofluorescence assay using primary antibodies α-SMA, Von Willebrand Factor (vWF) and S100A4 in order to characterize cancer associated fibroblasts and verify the contribution of endothelial to fibroblast transition. Non-pigmented samples were characterized by immunohistochemistry using primary antibodies pan-cytokeratin, vimentin, S100 and Melan A. Microvascular density was evaluated by immunofluorescent assay using vWF and by calculating total number of vessels in five 200x fields ("hotspots").S100A4 imunoexpression was calculated using K-means clustering segmentation method. Only one case showed α-SMA and vWF co-expression restricted to myofibroblasts in tumor stroma. The cells were predominantly peritumoral and periadnexal. S100A4 expression was significantly different among three histotypes with mixed melanomas displaying lesser percentage of positive cells. Some neoplastic cells mainly in spindle cell melanomas were also positive for S100A4. There were no significant differences between MVD/histotypes... (Complete abstract click electronic access below)
Mestre
7
Bedran, Telma Blanca Lombardo [UNESP]. "Efeito antimicrobiano e modulador da resposta imune dos peptídeos hBD-3 e LL-37 e dos polifenóis o chá verde e do cranberry." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/124090.
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000830081.pdf: 809941 bytes, checksum: ea53cd5ef0cec7fb993a2745e82dad53 (MD5)The antimicrobial peptides LL-37, hBD-1, hBD-2 and hBD-3 are considered an endogenous antibiotic, with important role in the prevention of periodontal diseases due to their ability to regulate the immune response. However those peptides could be degraded by periodontal pathogens. Therefore, therapies able to up regulate the secretion of those peptides by human cells, and the association of antimicrobial peptides with natural compounds, which may act in synergism to modulate the immune response, may be a novel approach for effectively controlling periodontal diseases. The aim of this in vitro study were: i) investigate the ability of green tea extract and EGCG to induce hBD-1 and hBD-2 secretion and gene expression by gingival epithelial cells (B11) and to protect hBDs from degradation by P. gingivalis, ii) A 3D co-culture model of gingival epithelial cells and fibroblasts stimulated with A. actinomycetemcomitans LPS (1 μg/ml) were used to investigated the anti-inflammatory properties of the hBD-3, LL-37, ACPACs and EGCG and to determine whether LL-37 acts in synergy with AC-PACs, EGCG and hBD-3. Gingival epithelial cells were stimulated with green tea extract or EGCG in the presence and absence of specific inhibitors. The secretion and gene expression of hBD-1 and hBD-2 was respectively measured by ELISA and qPCR. The ability of green tea extract and EGCG to prevent hBDs degradation by P. gingivalis present in a bacterial culture supernatant was evaluated by ELISA. A 3D co-culture model composed of gingival fibroblasts embedded in a collagen matrix overlaid with gingival epithelial cells had a synergistic effect with respect to the secretion of IL-6 and IL-8 in response to A. actinomycetemcomitans LPS stimulation compared to fibroblasts and epithelial cells individually. The 3D co-culture model was stimulated with noncytotoxic concentrations of: i) hBD-3 (10 and 20 μM) ...(Complete abstract electronic access below)
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Santos, Carolina Carvalho de Oliveira 1984. "Expressão e produção de IL-6, TNF-'alfa' e MCP-1 por fibroblastos (3T3) e odontoblastos (MDPC-23) após exposição a bactérias orais." [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289724.
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Orientador: Alexandre Augusto ZaiaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: A polpa dentária contém uma heterogeneidade de células, dentre elas destacam-se os fibroblastos e odontoblastos. Quando este tecido é agredido por micro-organismos ou seus bioprodutos, fibroblastos e odontoblastos secretam diversas citocinas inflamatórias para ativação do sistema imune, dentre estas TNF-'alfa', IL-6 e MCP-1. Este estudo avaliou a expressão gênica e a produção de citocinas inflamatórias após o contato in vitro das espécies Sreptococcus mutans, Porphyromonas gingivalis, Enterococcus faecalis e seus bioprodutos com odontoblastos e fibroblastos. A expressão gênica foi avaliada por RT-qPCR e as proteínas foram quantificadas por meio de citometria de fluxo, tipo CBA, nos períodos de 4, 8 e 24 horas. As bactérias estudadas promoveram sensibilização das células para expressão e produção das citocinas IL-6, TNF-'alfa', e MCP-1 principalmente nas primeiras 8 horas de contato. Tanto o contato direto com as bactérias como o contato com seus bioprodutos resultaram em estímulo para as células, contudo, o contato direto com as bactérias S. mutans e E. faecalis se mostrou mais eficiente para a estimulação de expressão e produção de citocinas. Por outro lado, o contato indireto com P. gingivalis mostrou ser mais efetivo para estimular a produção das citocinas. Desta forma, pode-se concluir que odontoblastos e fibroblastos são capazes de expressar e produzir citocinas pró-inflamatórias a partir de diferentes contatos quando estimulados por tipos bacterianos distintos.
Abstract: Dental pulp contains a heterogeneity of cells in its composition, among them stand out from fibroblasts and odontoblasts. When this tissue is attacked by bacteria or their by-products, fibroblasts and odontoblasts can secrete several inflammatory cytokines in order to attract and activate immune system to contain infectious agents. TNF-'alfa', IL-6 and MCP-1 are proteins secreted by fibroblasts and odontoblasts mainly involved in the origin and activation of the inflammatory process. This study aimed to evaluate gene expression and secretion of inflammatory cytokines after in vitro contact of bacteria Sreptococcus mutans, Porphyromonas gingivalis, Enterococcus. faecalis and its by-products with odontoblasts and fibroblasts. The proteins were quantified by flow cytometry type CBA and gene expression by Real Time - PCR in periods of 4, 8 and 24 hours. The results showed that the studied bacteria promoted sensitizing cells for expression and production of the cytokines IL-6, TNF-'alfa', MCP-1, particularly during the first 8 hours of contact. Both direct contact with bacterias or their by-products resulting in stimulation to the cells, however, direct contact with the bacteria S. mutans and E. faecalis was more efficient for stimulating expression and cytokine production. On the other hand, the indirect contact with P. gingivalis shown to be more effective to stimulate the production of cytokines. Thus, we may conclude that fibroblasts and odontoblasts are able to express and produce proinflammatory cytokines from different contacts when stimulated by different bacterial types
Doutorado
Endodontia
Doutora em Clínica Odontológica
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Silva, Giuliana Thaíse Araújo da. "Influência na variação da potência de irradiação por LED com tempo fixo em cultura fibroblástica L929." Universidade Federal de Goiás, 2018. http://repositorio.bc.ufg.br/tede/handle/tede/8540.
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The Light Emitting Diode (LED) is a semiconductor device that emits light source and can be used as a tissue modeler by means of the transformation of received photons. Photobiomodulation therapy (PBMT) is a specific term for the therapeutic application of light and acts as therapy, analgesia and anti-inflammatory. The objective of this work was to verify the effectiveness of LED at fixed time in the stimulation of fibroblasts. For this purpose, the L929 cell line submitted to LED irradiation (630 nm) was used, in triplicate, at the potency of 50, 75 and 100 mW, for five seconds and compared with non-irradiated control group. Next, cell viability, proliferation, nitric oxide production and collagen synthesis were observed. The results revealed that there was no cytotoxicity after 24, 48 and 72 hours of irradiation; there was an increase in the production of nitrite between the group of 72 hours and the other experimental groups and increase in the synthesis of collagen, directly proportional to the potencies used. Thus the irradiation allowed the fibroblastic stimulation with increased activity in the healing process.
O Diodo Emissor de Luz (Light Emissor Diode - LED) é um dispositivo semicondutor que emite fonte de luz e pode ser usado como modelador tecidual por meio da transformação de fótons recebidos. A fotobiomodulação (Photobiomodulation therapy - PBMT) é um termo específico para aplicação terapêutica da luz e atua como analgesia e anti-inflamatório. O objetivo deste trabalho foi de verificar a efetividade do LED em tempo fixo na estimulação de fibroblastos. Para tanto, utilizou-se a linhagem celular L929 submetida à irradiação LED (630 nm), em triplicata, nas potências de 50, 75 e 100 mW, por cinco segundos e comparou-se com grupo controle não irradiado. Em seguida, observou-se a viabilidade celular, proliferação, produção de óxido nítrico e síntese de colágeno. Os resultados revelaram que não houve citotoxicidade após 24, 48 e 72 horas de irradiação; houve aumento na produção de nitrito entre o grupo de 72 horas e os outros grupos experimentais e aumento na síntese de colágeno, diretamente proporcionais às potências utilizadas. Assim a irradiação possibilitou a estimulação fibroblástica com aumento de sua atividade no processo de cicatrização.
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Nogueira, Alessandra Fonseca Gambini. "Estudo in vitro do efeito de cones de obturação endodôntica na biomodulação de fibroblastos de ligamento periodontal." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/23/23156/tde-27112017-122839/.
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A obturação do canal radicular é uma etapa fundamental para o sucesso do tratamento endodôntico. É desejável que os materiais empregados nesta fase não interferiram negativamente com o reparo tecidual, mas preferencialmente estimulem a regeneração dos tecidos periapicais. Recentemente, cones de guta-percha combinados com material biocerâmico foram desenvolvidos com esta finalidade. Sendo assim, o objetivo deste estudo foi investigar o potencial citotóxico e biomodulador de cones de guta-percha convencionais, de cones de guta-percha contendo biocerâmica e de cones de polímero sobre células de ligamento periodontal in vitro. Cultura de fibroblastos de ligamento periodontal foi estabelecida a partir de terceiro molar humano. As células foram estimuladas com extratos de cones de guta-percha convencional, de cones de guta-percha contendo biocerâmica e de cones de polímero em diluição seriada para teste de viabilidade celular por meio do método MTT (Brometo de Difeniltetrazólio 3-(4,5-Dimetiltiazol-2-yl) após 72 h. Em seguida, a diluição de 1/5 foi empregada para estimulação das células por 72 h para detecção da expressão gênica de colágeno tipo I e proteína cementária 1 (CEMP-1) por RT-qPCR. Os dados foram estatisticamente analizados por meio de ANOVA sendo considerados significativos valores de p < 0,05. Os resultados observados de forma que, em extrato puro em extrato puro 1:1, houve comprometimento da viabilidade celular tanto para o extrato de cone de guta-percha quanto para o extrato do cone Cpoint podendo ser considerados citotóxicos. Nas outras diluições não houve diferença significativa neste parâmetro. Em relação à expressão gênica de colágeno, não foram observadas diferenças significativas quando da presença dos extratos. Para CEMP-1, significativa indução da expressão gênica foi observada para o cone de guta-percha. Conclui-se, através da análise dos resultados, que o cone de guta-percha e o cone de polímero são os mais citotóxicos em extrato puro, porém a guta-percha foi o único material que induziu uma expressão significativa de CEMP-1 que auxilia no reparo tecidual. O Col1 não foi induzido em nenhuma das amostras, porém também não foi inibido que indica que nenhum dos 3 tipos de cone interfere no reparo tecidual.Root canal obturation is a fundamental step for successful endodontic treatment. It is desirable that the materials employed at this stage did not adversely interfere with tissue repair but rather stimulate the regeneration of the periapical tissues. Recently, gutta-percha points combined with bioceramic materials were developed for this purpose. Thus, the objective of this study was to investigate the cytotoxic and biomodulatory potential of conventional gutta-percha points, gutta-percha points containing bioceramics and polymer points on periodontal ligament cells in vitro. Culture of periodontal ligament fibroblasts was established from one human third molar. The cells were stimulated with extracts of cones of conventional gutta-percha points, gutta-percha containing bioceramics and polymer points in serial dilution for cell viability test using the MTT assay [Diphenyltetrazolium Bromide 3- (4,5)]. Next, the 1/5 dilution was used to stimulate the cells for 72 h to detect the gene expression of type I collagen and cement protein 1 (CEMP-1) by RT-qPCR. Data were statistically analyzed by means of ANOVA being considered significant values of p <0.05. The results observed was that in a pure 1: 1 extract, there was impairment of cell viability for both the guta-percha cone extract and the Cpoint cone extract and could be considered cytotoxic. At the other dilutions, no significant difference on this parameter was observed. Regarding the gene expression of collagen, no significant differences were observed at the presence of extracts. For CEMP-1, significant induction of gene expression was observed for gutta-percha points. In conclusion, the analysis of the results showed that the gutta-percha and polymer points are the most cytotoxic at pure extract, however gutta-percha was the only material that induced a significant expression of CEMP-1 which assists the tissue repair. Col1 was not induced in any of the samples but was also not inhibited indicating that none of the 3 cone types interfere in tissue repair.
Books on the topic "Fibroblasts"
1
Kulkarni, Gajanan Vishwanath. Regulation of apoptosis in fibroblasts. [Toronto: University of Toronto, Faculty of Dentistry], 1996.
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2
Mueller, Margareta M., and Norbert E. Fusenig, eds. Tumor-Associated Fibroblasts and their Matrix. Dordrecht: Springer Netherlands, 2011. http://dx.doi.org/10.1007/978-94-007-0659-0.
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3
Brown, Denise Anne. Microtubule subpopulations in chick heart fibroblasts. Norwich: University of East Anglia, 1992.
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4
P, Phipps Richard, ed. Pulmonary fibroblast heterogeneity. Boca Raton: CRC Press, 1992.
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5
Symposium, Ciba Foundation. Fibrosis. London: Pitman, 1985.
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6
Turner, Neil A. The cardiac fibroblast. Kerala, India: Research Signpost, 2011.
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7
Karlsson, Christina. Negative growth control in normal human fibroblasts. Uppsala: Acta Universitatis Upsaliensis, 1995.
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8
Farsi, Jamila Mohamed Ali. Interactions of fibroblasts with extracellular matrix macromolecules. [Toronto: Faculty of Dentistry, University of Toronto, 1985.
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Chou, Debra Hsin-I. TNF-r̀egulation of phagocytosis in human gingival fibroblasts. Ottawa: National Library of Canada, 1995.
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Mueller, Margareta M. Tumor-Associated Fibroblasts and their Matrix: Tumor Stroma. Dordrecht: Springer Science+Business Media B.V., 2011.
Find full textBook chapters on the topic "Fibroblasts"
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Mack, Christopher. "Fibroblasts." In Atherosclerosis, 129–40. Hoboken, NJ: John Wiley & Sons, Inc, 2015. http://dx.doi.org/10.1002/9781118828533.ch11.
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Stewart, Alastair G., Lilian Soon, and Michael Schuliga. "Fibroblasts." In Inflammation and Allergy Drug Design, 149–62. Oxford, UK: Wiley-Blackwell, 2011. http://dx.doi.org/10.1002/9781444346688.ch11.
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Barcellos-Hoff, Mary Helen. "Fibroblasts." In Encyclopedia of Systems Biology, 739–40. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4419-9863-7_1393.
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Akers, lan A., Robin J. McAnulty, and Geoffrey J. Laurent. "Fibroblasts and myofibroblasts." In Cellular Mechanisms in Airways Inflammation, 159–98. Basel: Birkhäuser Basel, 2000. http://dx.doi.org/10.1007/978-3-0348-8476-1_6.
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Lapière, Ch M. "FIBROBLASTS AND FIBROCYTES." In Proceedings of the Third Symposium, Lyon, France, June 26–28, 1985, edited by Jacques Bienvenu, J. A. Grimaud, and Philippe Laurent, 369–74. Berlin, Boston: De Gruyter, 1986. http://dx.doi.org/10.1515/9783110860757-049.
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Kletsas, Dimitris. "Aging of Fibroblasts." In Aging of Cells in and Outside the Body, 27–46. Dordrecht: Springer Netherlands, 2003. http://dx.doi.org/10.1007/978-94-017-0669-8_3.
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Liao, Debbie, and Ralph A. Reisfeld. "Targeting Tumor Associated Fibroblasts Tumor Associated Fibroblasts and Chemotherapy." In Tumor-Associated Fibroblasts and their Matrix, 403–18. Dordrecht: Springer Netherlands, 2011. http://dx.doi.org/10.1007/978-94-007-0659-0_21.
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Zöller, N., and S. Kippenberger. "Influence of wIRA Irradiation on Wound Healing: Focus on the Dermis." In Water-filtered Infrared A (wIRA) Irradiation, 195–202. Cham: Springer International Publishing, 2022. http://dx.doi.org/10.1007/978-3-030-92880-3_16.
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AbstractImpaired wound healing, imbalanced fibroblast proliferation, and extracellular matrix synthesis are associated with aberrant scarring. The impact of impaired wound healing can be tremendous due to physical restrictions, high recurrence rates, stigmatization, and secondary infections in chronic wounds. It is therefore essential to develop alternative treatment regimens to those that are currently used. The highly diverse influence of water-filtered infrared-A (wIRA) on cell metabolism, bacterial colonisation, wound healing, and its high tissue penetration – reaching the subcutis without inducing harmful increases in skin surface temperature or pain – led to the investigation of the influence of the spectral and thermal component of wIRA on normal and keloid fibroblasts in vitro. Data show the potential value of the spectral and the thermal component of wIRA as an adjuvant therapy for aberrant scarring due to its differential influence on the proliferation, migration, and collagen type I synthesis of normal and keloid fibroblasts. The observed aspects in the context of hypertrophic scar treatment need to be evaluated in further basic research and clinical studies.
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Rodemann, H. Peter, and Hans-Oliver Rennekampff. "Functional Diversity of Fibroblasts." In Tumor-Associated Fibroblasts and their Matrix, 23–36. Dordrecht: Springer Netherlands, 2011. http://dx.doi.org/10.1007/978-94-007-0659-0_2.
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Hornby, A. E., and K. J. Cullen. "Mammary tumor fibroblasts are phenotypically distinct from non-tumor fibroblasts." In Experientia Supplementum, 249–71. Basel: Birkhäuser Basel, 1995. http://dx.doi.org/10.1007/978-3-0348-9070-0_13.
Full textConference papers on the topic "Fibroblasts"
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Holmes, Jeffrey W., and Thomas K. Borg. "Isotonic Biaxial Loading: An Economic, Versatile Method for the Study of Fibroblast-Populated Collagen Gels." In ASME 1999 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1999. http://dx.doi.org/10.1115/imece1999-0402.
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Abstract Studies of collagen gel contraction by embedded fibroblasts have characterized the response of free (unloaded) or isometric (maximally loaded) gels but not the response to intermediate loads. An inexpensive, simple system was devised to isotonically load fibroblast-populated collagen gels using freely hanging weights. This system provided excellent repeatability. Maximal contraction force was estimated at 1 mN per million cells in neonatal rat cardiac fibroblasts, a value that agreed well with reported isometric experiments in fibroblasts from other tissues. The ability to load uniaxially or biaxially and with variable loads will facilitate exploration of the regulation of fibroblast mechanics and biology by stress.
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Hung, Clark T., Fred D. Allen, Solomon R. Pollack, Eric T. Attia, Jo A. Hannafin, and Peter A. Torzilli. "Anterior Cruciate and Medial Collateral Ligament Fibroblasts Exhibit Different Ca2+ Responses to Fluid Flow." In ASME 1996 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 1996. http://dx.doi.org/10.1115/imece1996-1131.
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Abstract Injuries to the medial collateral ligament and anterior collateral ligament heal differently in vivo and this may be related to their response to physical forces. This hypothesis was tested by measuring the intracellular calcium concentration, [Ca2+]i, in canine MCL and ACL fibroblasts subjected to fluid flow (wall shear stress of 25 dynes/cm2). In experiments where a modified Hanks’ balanced salt solution perfusate was used, both cell types had a significant increase in [Ca2+]i compared to respective no-flow controls, MCL fibroblasts being nearly 2-fold greater than that of ACL fibroblasts. When 2% newborn bovine serum was added to the perfusate, ACL fibroblasts responded nearly 3-fold greater than MCL fibroblasts. The observed difference between the MCL and ACL fibroblast response to flow demonstrates that these cells are not the same.
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Dupuy, E., P. S. Rohrlich, and G. Tobelem. "HEPARIN STIMULATES FIBROBLAST GROWTH INDUCED BY PDGF." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643750.
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Heparin binds to smooth muscle cells and endothelial cells. It inhibits the proliferation of the smooth muscle cells and modulates the growth of endothelial cells. Fibroblasts which represent an other cell type belonging to the vascular wall could also have their growth modified by heparin. We have at first, demonstrated that 125I unfractionated heparin bigds to cultured human skin fibroblasts with a Kd of 1.16 10 M.A low molecular weight heparin fraction (PK 10169) competed (50 %)with I unfractionated heparin, but at aless extent than cold unfractionated heparin(90%).As it has been reported with endothelial and smooth muscle cells, about 30% of the bound unfractionated heparin was internalized bythe fibroblasts. Heparin alone at the concentration ranges from 0 to 10-5M has no effect on fibroblast proliferation measured by the H thymidine uptake. When the cellproliferation was induced by pure PDGF, heparin potentiated markedly the fibroblast growth.The effgct started at 10-8 M heparinand reached a plateau from 10-6 M to 10-5 M. Similar stimulationwas observed when the growth was induced by FGF or EGF. Low molecular weight heparin enhanced the fibroblast proliferation induced by PDGF but at a less extent than unfractionated heparin, chondroltin sulfate has no effect. When added during the cell culture growth withhuman serum (5%), unfractionated heparin increased by 48 the cell proliferation as measured bycell counting at the 6th day of the culture. PDGF did not modify the heparin binding on fibroblast cultures either at 4°C or 37°C and did not alter the process of heparin internalization. JDGF binding to the cultured fibroblast (Kd 10.1 ± 3.4 10-10 M)was not modified by the presence of heparin when studied at 4°C.In conclusion : i) cultured human fibroblasts bind and internalize heparin, ii) heparinand heparin fraction stimulate the fibroblastgrowth induced by PDGF, iii) since the binding of PDGF is not modified by bound heparin, the mechanism of stimulation remains unknown.
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Hurley, Jennifer R., and Daria A. Narmoneva. "Fibroblasts Induce Mechanical Changes in the Extracellular Environment and Enhance Capillary-Like Network Formation." In ASME 2008 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2008. http://dx.doi.org/10.1115/sbc2008-193093.
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Cardiac tissue engineering studies have demonstrated the importance of revascularization in engineered grafts for successful implantation and regeneration [1]. Understanding the myocardium’s complex cellular organization and the interactions between the major cardiac cell types (cardiomyocytes, endothelial cells, and cardiac fibroblasts) is critical for revascularization. Our previous studies have shown the importance of cardiomyocyte-endothelial interactions [2]. However, there is limited information available on endothelial-fibroblast interactions. We and others have previously observed that during capillary assembly, fibroblasts provide chemical signaling via expression of growth factors [3, 4]. In addition, fibroblasts may also regulate angiogenesis through alterations to the mechanical environment via myocardial remodeling, including matrix degradation and deposition, and tissue contraction. Changes to the extracellular mechanical enviroment may lead to changes in basic cell functions such as proliferation, apoptosis, and growth factor expression.
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Lee, Sheng-Lin, Kenneth M. Pryse, Boyd Butler, Elliot L. Elson, and Guy M. Genin. "Mechanically-Induced Cytoskeletal Remodeling in 3D Cultures of Contractile Fibroblasts." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19684.
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Fibroblasts are responsible for collagen biosynthesis and organization in connective tissues, and play a role in regulation of epithelial differentiation, regulation of inflammation, and wound healing. Increasing evidence suggests that fibroblast might promote tumors by facilitating angiogenesis and cancer progression [1]. They are coupled mechanically to their fibrillar extra-cellular matrix, which can regulate cell behavior through its composition and mechanics.
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Clezardin, P., and J. L. McGregor. "STRUCTURAL AND FUNCTIONAL COMPARISON OF THROMBOSPONDIN FROM PLATELETS, ENDOTHELIAL CELLS AND FIBROBLASTS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643819.
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Thrombospondin (TBSP) is a 450 kDa glycoprotein secreted by a wide range of cells including platelets, endothelial cells and fibroblasts. Using non-denaturating conditions, we recently reported that platelet TBSP was structurally different from endothelial and fibroblast TBSP (P. Clezardin et al., Eur. J. Biochem., 1986, 159, 569-579). The aim of this study was to compare the structure of TBSP purified from platelets, endothelial cells and fibroblasts using denaturating conditions. Moreover, the interaction of fibrinogen with these three forms of TBSP was also investigated. TBSPs were first purified by heparin-Sepharose and immunoaffinity chromatography followed by Mono O anion-exchange chromatography on a FPLC system. Thermolysin digests of purified TBSPs were analysed by SDS-polyacrylamide gel electrophoresis under reducing conditions and the subsequent electrophoresed proteolytic fragments identified by Coomassie and silver staining. The interaction of undigested and digested TBSPs with solid-phase adsorbed fibrinogen was investigated by enzyme-linked immunosorbent assay using an anti-TBSP monoclonal antibody (P10). when using Coomassie staining, a 70 kDa proteolytic fragment of thermolysin-treated platelet TBSP was absent from the endothelial and fibroblast TBSP digests. Moreover, a 18 kDa fragment from thermolysin-treated endothelial and fibroblast TBSP was undetectable in the platelet TBSP digest when using silver staining on SDS-polyacrylamide gels. The binding of undigested TBSPs to solid-phase adsorbed fibrinogen was different from that obtained with digested TBSPs. These results indicate that the observed structural differences might induce functional differences between platelet and the two other forms of TBSP.
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Hurley, Jennifer R., and Daria A. Narmoneva. "Endothelial-Fibroblast Interactions in Angiogenesis and Matrix Remodeling." In ASME 2009 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2009. http://dx.doi.org/10.1115/sbc2009-206534.
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Revascularization is critical for successful regeneration of ischemic cardiac tissue after injury. To achieve revascularization in engineered cardiac grafts, it is necessary to understand the interactions between major cardiac cell types. The importance of cardiomyocyte-endothelial interactions in angiogenesis is well documented [1]; however, less is known about interactions between endothelial and stromal cells, fibroblasts in particular. Studies indicate that during capillary assembly, fibroblasts (FBs) provide chemical signaling via growth factor expression and endothelial activation and proliferation [2]. In addition, fibroblasts deposit extracellular matrix (ECM) proteins [3] and also play a role in matrix remodeling. The objective of our study was to further investigate the role of endothelial-fibroblast interactions in angiogenesis with a focus on FB regulation of the extracellular mechanical environment. We and others have recently shown that self-assembling peptide nanoscaffold is a promising material for cardiac tissue regeneration, enhancing angiogenesis in vitro and promoting tissue neovascularization in vivo [1, 4–5]. An important advantage of this nanoscaffold is the ability to control its material properties, such as stiffness and rate of MMP degradation, through its sequence and/or concentration [6]. In this study, RAD16-II peptide nanoscaffold was used as a controlled system to test the hypothesis that fibroblasts regulate angiogenesis via modifying the extracellular mechanical environment through mechanisms including cell-mediated scaffold disruption and matrix remodeling.
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Larsson-Callerfelt, Anna-Karin, Annika Andersson Sjöland, Oskar Hallgren, Mariam Bagher, Lena Thiman, Claes-Göran Löfdahl, Leif Bjermer, and Gunilla Westergren-Thorsson. "VEGF induces ECM synthesis and fibroblast activity in human lung fibroblasts." In ERS International Congress 2017 abstracts. European Respiratory Society, 2017. http://dx.doi.org/10.1183/1393003.congress-2017.pa1045.
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De Jesus, Aribet M., Maziar Aghvami, and Edward A. Sander. "Fibroblast-Mediated Fiber Realignment in Fibrin Gels." In ASME 2013 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/sbc2013-14385.
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When fibroblasts are added to a fibrin gel, the cells rapidly compact the gel and produce a fiber alignment pattern that depends in part on the cell traction forces, gel geometry, and gel mechanical constraints [1]. Over time the fibrin is digested and replaced with cell synthesized collagen and other extracellular matrix (ECM) proteins that follow the initial alignment pattern of the gel [2]. This remodeling process proceeds in a complex and integrated manner that is influenced by the mechanical environment [3]. In order to better understand fibroblast-fibrin interactions and the remodeling process, we obtained time-lapse images of the development of fiber alignment between clusters of dermal fibroblasts (i.e., explants) in a fibrin gel. The experimental results were then compared to a model that incorporated the effects of traction forces on ECM reorganization.
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Guzy, R., B. Ansbro, E. Reed, and N. O. Dulin. "Fibroblast Growth Factor 2 Accelerates Myofibroblast Dedifferentiation in Primary Human Lung Fibroblasts." In American Thoracic Society 2020 International Conference, May 15-20, 2020 - Philadelphia, PA. American Thoracic Society, 2020. http://dx.doi.org/10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a4042.
Full textReports on the topic "Fibroblasts"
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Chang, Howard Y. Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin. Fort Belvoir, VA: Defense Technical Information Center, June 2008. http://dx.doi.org/10.21236/ada487344.
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Tsao, Hensin. Governance of Cutaneous Photocarcinogenesis by Chronic UVA-Exposed Dermal Fibroblasts. Fort Belvoir, VA: Defense Technical Information Center, September 2014. http://dx.doi.org/10.21236/ada612449.
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Chang, Howard Y. Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin. Fort Belvoir, VA: Defense Technical Information Center, June 2009. http://dx.doi.org/10.21236/ada506474.
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Reisfeld, Ralph A. Immunotherapy Targeting Tumor Stromal Fibroblasts Improves Chemotherapy of Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, February 2007. http://dx.doi.org/10.21236/ada466673.
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Chang, Howard Y. Site-Specific Differentiation of Fibroblasts in Normal and Scleroderma Skin. Fort Belvoir, VA: Defense Technical Information Center, June 2010. http://dx.doi.org/10.21236/ada544405.
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McCormick, J. J. Malignant transformation of diploid human fibroblasts by transfection of oncogenes. Office of Scientific and Technical Information (OSTI), January 1992. http://dx.doi.org/10.2172/6852538.
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Georgiev, Georgi, Rossitza Konakchieva, Albena Momchilova, and Roumen Pankov. Quiescent Primary Fibroblasts Sequester Activated ERK1/2 into the Lipid Rafts. "Prof. Marin Drinov" Publishing House of Bulgarian Academy of Sciences, March 2020. http://dx.doi.org/10.7546/crabs.2020.03.09.
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Mrksich, Milan. Design of Substrates to Study the Interactions of Tumor Cells and Fibroblasts. Fort Belvoir, VA: Defense Technical Information Center, August 2001. http://dx.doi.org/10.21236/ada417979.
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J.P, Babu. Long-term dental adhesive toxicity on human gingival fibroblasts and epithelial cells. Science Repository, June 2019. http://dx.doi.org/10.31487/j.dobcr.2019.03.01.
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Milo, G. Chemical Carcinogen (Hydrazine et al.) Induced Carcinogenesis of Human Diploid Fibroblasts in vitro. Fort Belvoir, VA: Defense Technical Information Center, June 1985. http://dx.doi.org/10.21236/ada158974.
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