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1
Yi, Ming. "Extracellular matrix proteins and angiogenesis /". Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3091204.
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2
Wendel, Mikael. "Skeletal tissue proteins isolation and characterization of novel extracellular matrix proteins /". Lund : Dept. of Medical and Physiological Chemistry, University of Lund, 1994. http://books.google.com/books?id=zvtqAAAAMAAJ.
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3
Chan, Cheuk-ming. "Controlled protein release from collagen matrix". Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B3955868X.
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4
Avella, Charlotte Sinclair. "Strain related differential regulation of tendon extracellular matrix proteins". Thesis, Royal Veterinary College (University of London), 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558956.
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Garcia, John Francis. "The role of extracellular matrix proteins in epithelial tumorigenesis /". May be available electronically:, 2008. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
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Shen, Zhenxin. "Expression and localization of extracellular matrix proteins in skeletal development". Lund : Dept. of Cell and Molecular Biology, Section for Connective Tissue Biology, Lund University, 1998. http://books.google.com/books?id=Xe9qAAAAMAAJ.
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St, John Joni J. Cheung H. Tak. "Characterization of the adhesion of lymphocytes to extracellular matrix proteins". Normal, Ill. Illinois State University, 1989. http://wwwlib.umi.com/cr/ilstu/fullcit?p8918625.
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Thesis (Ph. D.)--Illinois State University, 1989.Title from title page screen, viewed October 12, 2005. Dissertation Committee: H. Tak Cheung (chair), David W. Borst, Herman E. Brockman, Arlan G. Richardson, Brian J. Wilkinson. Includes bibliographical references (leaves 145-156) and abstract. Also available in print.
8
Burnier, Julia. "Regulation of site-specific liver metastasis by extracellular matrix proteins". Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86657.
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Metastatic disease remains the main cause of death from cancer. Few therapeutic options for patients have demonstrated potential in curing metastatic disease. The molecular mechanisms underlying site-specific metastasis and the factors mediating tumor cell homing remain largely unknown. Based on a murine Lewis lung carcinoma tumour model of site-specific metastasis mediated by the expression of the insulin-like growth factor - I receptor (IGF-IR), we identified ECM components that show particular promise in regulating metastasis to a specific site. Specifically, we identified collagen IVα1 and α2 as differentially expressed in liver- and lung-colonizing cells. The overexpression of these genes caused major changes to cell structure and function including differences in cellular morphology, anchorage-independent growth, and resulted in a switch from a lung- to a liver-metastasizing phenotype. These changes were at least in part due to α2-integrin-mediated activation of focal adhesion kinase (FAK) and protection from anoikis. Collagen IV α1 suppression resulted in increased anoikis and decreased tumour cell colonization of the liver, making it an essential and sufficient gene in liver metastasis in our model. Moreover, type IV collagen overexpression resulted in major changes to ECM and ECM-degradation genes decreasing MMP-3, MMP-9, MMP-13, and collagen type III. Uveal melanoma cells with distinct metastatic phenotypes also showed major changes to these genes. Finally, by analyzing human specimens of metastatic disease, collagen IV was shown to be expressed only in metastatic and specifically hepatic metastases when compared to primary tumours and metastases to other organs. Collectively, these findings implicate collagen IV as a clinically relevant marker and potential target against site-specific metastasis to the liver.Le cancer métastatique ne présente que peu d'options thérapeutiques et de ce fait constitue la cause principale de décès chez les patients qui en sont atteints. Par ailleurs, les mécanismes moléculaires responsables de l'atteinte d'organes-cibles de la métastase par les cellules cancéreuses demeurent largement méconnus. La thèse qui suit présente l'identification d'un marqueur moléculaire qui apparait comme étant un facteur crucial dans l'atteinte des organes-cibles par les cellules métastatiques. En effet, la constituante de la matrice extracellulaire collagene IVα1 et α2, semble être exprimée de manière distinctive chez les cellules colonisant le foie et les poumons. Nous basant sur un modèle murin de métastase provenant de carcinome pulmonaire et véhiculée par l'expression de IGF-IR, nous avons identifié des changements majeurs quant à la structure et à la fonction des cellules cancéreuses, suite à la surexpression des gènes du Collagene IVα1 et α2. Ces changements comprennent, entre autre, des différences au niveau de la morphologie et la croissance cellulaire et ont aussi pour résultat la mutation du phénotype métastatique de pulmonaire à hépatique. Ces changements sont en partie conséquence de l'activation de la kinase d'adhésion focale (FAK) et de la protection de l'anoikis. Par contre, la suppression de l'expression du Collagène IV accroit l'anoikis et diminue la colonisation du foie par les cellules cancéreuses. En outre, la surexpression du Collagène IV apporte des changements majeurs au niveau de la matrice extracellulaire et aux gènes de dégradation de celle-ci, diminuant MMP-3, MMP-9, MMP-13 et le collagène III. Les cellules de mélanome uvéale à phénotype métastatique distinct présentent aussi des changements importants quant à l'expression ces gènes. Finalement, après analyse de spécimens humains, le collagène IV semble être exprimé exclusivement au niveau des tumeurs métastatiques et en
9
Chan, Cheuk-ming, e 陳卓銘. "Controlled protein release from collagen matrix". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B3955868X.
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Xu, Qian Angela. "Matrix proteins gene expression by mesenchymal cells". Thesis, The University of Sydney, 1997. https://hdl.handle.net/2123/27663.
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Chondrocytes from articular cartilage (AC) of diarthrodial joints and smooth muscle cells (SMCs) derived from blood vessels are both of mesenchymal origin. In this study, the mRNA expression by these cells of matrix proteoglycan (PG) and collagen was examined in vitro and in vivo. Since the expression of matrix components by mesenchymal cells is influenced by their interaction with growth factors and cytokines, experiments were also undertaken in vitro to determine the effect of transforming growth factor B1 (TGF-B1) and interleukin -1B (IL-1B) on PG and collagen gene expression by these cells.
11
Davies, Huw Alun. "A family of glycoproteins from the petioles of Brassica campestris with potential roles in plant development and stress responses". Thesis, University of East Anglia, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317996.
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Matias, Marie Anne Teresa J. "Immunohistochemical localization of extracellular matrix proteins of the periodontium during cementogenesis /". [St. Lucia, Qld.], 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe16347.pdf.
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Yu, Xuefeng. "Mechanism of osteoclast migration : effect of chemoattractant cytokines, extracellular matrix proteins, and proteinase inhibitors". Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287659.
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Hunter, Morgan Campbell. "Analysis of the interaction of Hsp90 with the extracellular matrix protein fibronectin (FN)". Thesis, Rhodes University, 2014. http://hdl.handle.net/10962/d1020960.
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Mounting evidence suggests that Hsp90 is present and functionally active in the extracellular space. The biological function of extracellular Hsp90 (eHsp90) remains relatively uncharacterized compared to that of intracellular Hsp90. eHsp90 has been shown to interact with a finite number of extracellular proteins, however, despite the identification of eHsp90 interacting proteins, the function of eHsp90 in these complexes is unknown. Several reports suggest a role for eHsp90α in cell migration and invasion. Reported targets for eHsp90 stimulated cell migration include MMPs, LRP-1, tyrosine kinase receptors and possible others unidentified. Limited studies report a role for eHsp90β. Recently, Hsp90α and Hsp90β were isolated in a complex containing fibronectin (FN) on the surface of MDA-MB-231 breast cancer cells. Herein, we report direct binding of Hsp90α and Hsp90β to FN using a solid phase binding assay and surface plasmon resonance (SPR) spectroscopy. SPR spectroscopy showed that Hsp90β bound the 70 kDa amino-terminal fragment of FN (FN70), but that binding of FN to Hsp90β was not limited to FN70. Confocal microscopy showed regions of colocalization of Hsp90 with extracellular FN matrix fibrils in Hs578T breast cancer cell lines. Treatment of Hs578T breast cancer cells with novobiocin (an Hsp90 inhibitor) and an LRP-1 blocking antibody resulted in a loss of FN matrix and FN endocytosis (novobiocin treated). Addition of exogenous Hsp90β was able to recover such effect after both treatments. FN was shown to colocalize with intracellular LRP-1 in novobiocin treated Hs578T cells. Immunoprecipitation of an LRP-1 containing complex showed the presence of Hsp90 and 70 and 120+ kDa FN fragments. Treatment of Hs578T cells with novobiocin increased the level of FN120+ bound in LRP-1 immunoprecipitate. Exogenous Hsp90β decreased the level of low and high molecular weight FN fragments in a complex with LRP-1, despite the fact that higher levels of lower molecular weight FN fragments were detected in this cell lysate compared to the other treatments. We report FN as a novel interacting protein of eHsp90. Taken together, we provide evidence for a direct role of eHsp90β in FN matrix remodeling. We suggest that Hsp90 plays a direct role in FN matrix dynamics through interaction with FN and LRP-1. The identification of FN as a novel interacting protein of eHsp90 suggests a role for Hsp90 in FN matrix remodeling, which is important for a number of fundamental cellular processes including cell migration and metastasis.
15
Seyfried, Nicholas T. "The structure and function of hyaluronan-binding proteins in extracellular matrix assembly". Thesis, University of Oxford, 2004. http://ora.ox.ac.uk/objects/uuid:e1a2cf8f-7ac7-4c5a-bd3f-53d7653e8888.
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The chondroitin sulfate proteoglycan (CSPG) aggrecan forms link protein-stabilised complexes with hyaluronan (HA), via its N-terminal G1-domain, that provide cartilage with its load bearing properties. Similar aggregates (potentially containing new members of the link protein family), in which other CSPGs (i.e., versican, brevican and neurocan) substitute for aggrecan, may contribute to the structural integrity of many other tissues including skin and brain. In this thesis, cartilage link protein (cLP) and the G1-domains of aggrecan (AG1) and versican (VG1) were expressed in Drosophila S2 cells, purified to homogeneity and functionally characterised. The recombinant human proteins were found to have properties similar to those described for the native molecules. For example cLP formed dimers, and HA decasaccharides (HA 10-mers) were the minimum size that could compete effectively for their binding to polymeric HA. In addition, gel filtration and protein cross-linking/MALDI-TOF peptide fingerprinting showed that cLP and AG1 interact in the absence or presence of HA. Conversely, cLP and VG1 did not bind directly to each other hi solution yet formed ternary complexes with HA24. N-linked glycosylation of VG1 and AG1 was demonstrated to be unnecessary for either HA binding or the formation of ternary complexes. Additionally, the length of HA required to accommodate two G1-domains was found to be significantly larger for aggrecan than versican, which may reflect differences hi the conformation of HA stabilised on binding these proteins. To further investigate protein-HA interactions, fluorescent HA oligosaccharides were prepared and characterised. HA oligosaccharides labelled with the fluorophore 2-aminobenzoic acid (2AA) from four to 40 residues hi length were purified to homogeneity by ion exchange chromatography using a logarithmic gradient. Molecular weight and purity characterisation of HA oligosaccharides was facilitated by 2AA derivitisation since it enhanced signals in MALDI-TOF mass spectrometry and improves fluorophore-assisted carbohydrate electrophoresis (FACE) analysis by avoiding the inverted parabolic migration characteristic of 2-aminoacridone (AMAC) labelled sugars. The small size and shape of the fluorophore maintains the biological activity of the derivatised oligosaccharides, as demonstrated by their ability to compete for polymeric hyaluronan binding to VG1, AG1 and cLP. An electrophoretic mobility shift assay was used to study VG1 binding to 2AA-labelled HA 8-, 10-, 20-, 30- and 40-mers and although no stable VG1 binding was observed to labelled 8-mers, the equilibrium dissociation constant (100 nM) for VG1 with HA 10-mers was estimated from densitometry analysis of the free oligosaccharide. Interactions involving 2AA labelled HA 20-, 30-, and 40-mers with VG1 also displayed positive cooperativity. Therefore, oligosaccharides labelled with 2-aminobenzoic acid are biologically active and show excellent potential as probes in fluorescence-based assays that investigate protein-carbohydrate interactions.
16
Taylor, Mary Louise. "Extracellular Matrix Proteins of the Nurse Cell Capsule in Trichinella spiralis Infections". PDXScholar, 1994. https://pdxscholar.library.pdx.edu/open_access_etds/4782.
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The infectious first-stage larvae of the nematode Trichinella spiralis is an intracellular parasite of altered skeletal muscle. Invasion of the muscle cell initiates a series of morphological changes in the host muscle cell which ultimately results in a specialized unit called the nurse cell. The completed nurse cell consists of a collagenous capsule, matrix of altered sarcoplasm, and a circulatory rete. The purpose of this study was to determine the types of collagen present in the nurse cell capsule. Additionally, the presence of the gl ycoproteins, laminin and tenascin was determined. This study also sought to demonstrate the location of the selected extracellular matrix proteins within the capsule. Nurse cells were isolated from infected host muscle by sequential protease treatment with pronase, collagenase, and hyaluronidase. Nurse cells were digested with pepsin to produce characteristic pepsin-resistant triple helical fragments of collagen. The nurse cellpepsin digest was characterized by SDS-page, under reduced and nonreduced conditions, with type VI collagen and the ala2a3 chains of type XI collagen. Frozen tissue sections of infected and non-infected rat diaphragms were screened with specific polyclonal antibodies against types I, m, IV, V/Xl, and VI collagen, laminin, and tenascin. Indirect immunofluorescence using FITC secondary antibodies was used to locate the protein in the capsule and host tissue. SDS-page of the nurse cell-pepsin digest produced an electrophoretic pattern of resistant fragments characteristic for types I, III, IV, V, and VI collagen. Additionally, fragments migrated with an apparent molecular weight expected for pepsin resistant fragments of laminin. Indirect immunofluorescence showed types I, III, IV, and VI collagen, and laminin were distributed throughout the capsule. Serum No. 4876, which recognizes type V /XJ collagen, localized to the larvae. Tenascin failed to stain the nurse cell or host tissue. The results show that the capsule is a heterogenic structure with types I, III, IV, V, and VI collagens, and laminin distributed throughout the structure. The immunolocalization of Serum No. 4876 to the larvae suggests that a nematode collagen shares an amino acid sequence in common with mammalian type V /XI collagen.
17
Al, Ramadan Saeed Yaseen. "Analysis of some novel uterine extracellular matrix proteins and a growth factor". [College Station, Tex. : Texas A&M University, 2007. http://hdl.handle.net/1969.1/ETD-TAMU-1383.
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18
Xia, Ying. "Influence of extracellular matrix proteins on expression of proteinases in endothelial cells /". [S.l.] : [s.n.], 2001. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=14024.
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McFarlane, Ainsley Alana Carole. "Structural and functional characterization of the extracellular matrix proteins COMPcc and NtA". Elsevier, 2009. http://hdl.handle.net/1993/4837.
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The extracellular matrix (ECM) is a complex of proteins and carbohydrates that not only provides a structural support between tissues but also functions in a wide variety of cellular activities. ECM proteins are large, complex proteins with many repeating domains. Individual domains can be analyzed for the investigation of structure-function relationships. This thesis focuses on two ECM proteins of interest: N-terminal agrin (NtA) and the coiled-coil domain of cartilage oligomeric matrix protein (COMPcc). Agrin is an important ECM protein involved in postsynaptic differentiation at the neuromuscular junction, mediated by binding in the NtA domain. In agrin, the NtA domain is followed by nine follistatin-like (FS) domains. Structural studies showed a novel interdomain disulfide bridge between the NtA and first FS domain in agrin. This disulfide bridge compensates for a seven residue splice insert in the C-terminus of NtA, suggesting that the interdomain disulfide bond may be necessary for the proper folding of agrin.
COMP is another important ECM protein that is found in cartilage, tendon, and ligament. It is a homopentamer held together by disulfide bonds in the central coiled-coil oligomerization domain. Previous structural studies demonstrated that COMPcc forms a pentameric α-helical coiled-coil structure containing a 73Å-long cavity with a diameter of 2–6Å that is capable of binding hydrophobic compounds. This binding capacity of COMPcc was investigated and the high-resolution crystal structures of COMPcc in complex with five naturally-occurring fatty acids were solved. Additionally, the binding properties of COMPcc in solution were investigated through the use of fluorescence spectroscopy. Both the x-ray crystallographic and solution data reveal that binding favourability of fatty acids to COMPcc is driven by length of the methylene tail and degree of unsaturation. These results suggest the possibility of COMPcc to be used in targeted drug delivery systems.
20
Yaka, Cane. "Studies of axonal regeneration on a grid pattern of extracellular matrix proteins". Thesis, Uppsala universitet, Institutionen för neurovetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-205230.
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Ichikawa, Takafumi. "Roles of vinexin family proteins in sensing the stiffness of extracellular matrix". Kyoto University, 2017. http://hdl.handle.net/2433/225957.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第20587号
農博第2239号
新制||農||1052(附属図書館)
学位論文||H29||N5076(農学部図書室)
京都大学大学院農学研究科応用生命科学専攻
(主査)教授 植田 和光, 教授 矢﨑 一史, 教授 宮川 恒
学位規則第4条第1項該当
22
Degendorfer, Georg. "Mechanisms and Biological Consequences of Damage to Extracellular Matrix Proteins by Peroxynitrite". Thesis, The University of Sydney, 2015. http://hdl.handle.net/2123/14554.
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Peroxynitrite (ONOO–) is a potent oxidizing and nitrating agent, formed under inflammatory conditions by the diffusion-controlled reaction of superoxide radicals (O2•–) with nitric oxide (•NO). This species reacts rapidly, via both non-radical and radical reactions, with proteins resulting in protein damage. As there are limited antioxidant and repair enzymes extracellularly, damage to extracellular matrix (ECM) proteins is likely to persist and accumulate over time. However, there is a lack of detailed mechanistic information on how ONOO– oxidation and nitration affects ECM proteins. This Thesis investigates the significance of these reactions and how this modulates the structure and function of three different isolated ECM proteins, laminin-111, plasma fibronectin, recombinant tropoelastin and a complex mixture of basement membrane proteins. Exposure of ECM proteins to ONOO– at physiological relevant concentrations (10 μM) lead to protein aggregation and fragmentation. Significant amounts of nitration products (3-nitroTyr, 6-nitroTrp) in the millimolar-range and depletion of corresponding parent Tyr and Trp were detected on all analysed ECM proteins with this effect being modulated by CO2. Furthermore biological function and activity was compromised post ONOO– exposure. Overall, the studies presented in this Thesis provide new information about the reactivity of ONOO– with ECM proteins, and how this affects the structure and the function of these proteins.
23
Leung, Ho-chuen, e 梁浩銓. "A study of H5N1-M2e-based universal influenza vaccine". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208568.
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The ectodomain of influenza matrix protein 2 (M2e) may be an ideal candidate in the development of influenza universal vaccine due to its highly conserved property among different subtypes/strains of influenza virus. M2e based vaccines have been extensively studied and potent cross-subtype/strain protections have been reported. However, more and more M2e mutants of influenza virus have been identified in recent years. It is still unclear whether M2e based vaccines are effective against these M2e mutants of influenza virus.
This study first evaluated cross-protection of an M2e tetrameric peptide vaccine based on H5N1 virus strain A/Vietnam/1194/04 (VN/1194-M2e) against lethal challenges of M2e mutants of H5N1 virus strain A/Hong Kong/156/97 (HK/156) and a novel H7N9 virus, because there are 3 or 5 amino acid differences between VN/1194-M2e and HK/156-M2e or VN/1194-M2e and H7N9-M2e. The results showed that the vaccination of VN/1194-M2e did not induce high level of cross-reactive antibodies against HK/156-M2e and just provided poor cross-protection against lethal challenge of HK/156 virus. In contrast, VN/1194-M2e vaccination induced high level of cross-reactive antibodies against H7N9-M2e. Consistently, the vaccination provided good cross-protection against lethal challenge of H7N9 virus. These results strongly suggested that some mutations in M2e, such as mutations at positions 10, 14 and 16 which found in HK/156 M2e, might affect the M2e vaccine efficacy, but some others, such as five mutations found in H7N9-M2e, might not be critical for the M2e immunogenicity.
This study then investigated the relationship between the M2e immunogenicity and amino acid mutations of the M2e. Beside VN/1194-M2e (P0), we synthesized additional 10 M2e mutant peptides which contain different single or multiple mutations. The 3D structures of these M2e peptides were predicted and analyzed. The prediction results showed that group 1 peptides (P0, P10, P14, P16, P18, P20 and P18-20) exhibited either irregular structures or loose hairpin structures which might associate with well exposure of antigenic epitope, whereas group 2 peptides (P10-14, P10-16, P14-16 and P10-14-16) formed tight hairpin structures in which antigenic epitope might bury inside their own secondary structure. Vaccination efficacies of these M2e peptides were evaluated in mice for antibody responses and cross-protection against lethal challenge of VN/1194 and HK/156 viruses. Our results showed that vaccinations of group 1 peptides induced high levels of cross-reactive antibodies against VN/1194-M2e and good cross-protection against lethal challenge of VN/1194 virus. However, vaccinations of group 2 peptides vaccinations induced significantly lower VN/1194-M2e antibody responses and poor cross-protection against lethal challenge of VN/119 virus. Furthermore, both group 1 and group 2 peptides could just induce low levels of cross-reactive antibodies against HK/156-M2e and poor protection against lethal challenge of HK/156 virus.
Although H5N1-M2e tetrameric peptide has been previously shown to protect mice from lethal challenges by different subtypes/strains of influenza virus, this study has shown that certain amino acid variations in M2e could weaken M2e immunogenicity but some others might not. The different secondary structures of M2es may probably associate with their immunogenicity. Our findings have provided valuable information for the development of M2e based universal vaccines.published_or_final_version
Microbiology
Doctoral
Doctor of Philosophy
24
Woo, Wei-Meng. "Roles of epidermal cytoskeleton and extracellular matrix proteins in Caenorhabditis elegans embryonic morphogenesis /". Diss., Digital Dissertations Database. Restricted to UC campuses, 2005. http://uclibs.org/PID/11984.
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Pohjolainen, V. (Virva). "Characterization of non-collagenous extracellular matrix proteins in cardiac and aortic valve remodelling". Doctoral thesis, Oulun yliopisto, 2012. http://urn.fi/urn:isbn:9789514299025.
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Abstract Heart failure (HF) and aortic valve stenosis (AS) are complex disorders affected by functional alterations and actively regulated remodelling of the heart and the aortic valve, respectively. In addition to structural proteins, such as collagens and elastin, the extracellular matrix (ECM) in the heart and the aortic valve comprises non-collagenous factors that are not strictly involved in the architecture but may modulate cardiac and valvular remodelling. In the present study the expression of non-collagenous fibrosis- and calcification-related ECM proteins was investigated in HF-associated cardiac remodelling from different origins as well as in fibrocalcific aortic valve disease leading to AS. The experimental models of pressure overload, myocardial infarction (MI) and chronic renal failure were used to study the cardiac expression of bone morphogenetic protein (BMP)-2, BMP-4, bone sialoprotein, matrix Gla protein (MGP), osteoactivin, osteopontin, periostin and/or pleiotrophin in vivo in cardiac remodelling. Human aortic valves, obtained from patients undergoing valve replacement, were studied to characterize the valvular expression of BMP-2, BMP-4, bone sialoprotein, MGP, osteoactivin, osteopontin, osteoprotegerin, periostin, pleiotrophin, and thrombospondins (TSPs) 1-4 in the different stages of fibrocalcific aortic valve disease. Left ventricular (LV) MGP expression was upregulated in vivo in non-uremic cardiac remodelling. In vitro results indicate that angiotensin II elevates MGP expression in cardiomyocytes and fibroblasts. Periostin gene expression was induced in cardiac but not in aortic valve remodelling and the cardiac induction in chronic renal insufficiency was associated with LV hypertrophy and blood pressure as well as the cardiac gene expression of other fibrosis-related genes. Bone sialoprotein and osteopontin were expressed in the aortic valves in parallel with calcification, and also in distinct models of cardiac remodelling. Osteoprotegerin protein expression in stenotic valves was weak regardless of a simultaneous increase in gene expression. BMPs were downregulated in AS and no change in LV gene expression was detected in uremic cardiac remodelling. All the studied TSPs were expressed in human aortic valves, and especially the expression of TSP-2 was shown to increase in fibrocalcific aortic valves simultaneously with decreased activation of the Akt/nuclear factor (NF)-κB-pathway. This study delineates distinct expression patterns of non-collagenous ECM proteins in pathological tissue remodelling in the heart and in the aortic valve, and thus emphasizes the role of ECM proteins as an important modulator of cardiac and aortic valve remodellingTiivistelmä Sydämen vajaatoiminnan ja aorttastenoosin taudinkuvaan kuuluvat toiminnallisten muutosten ohella aktiivisesti säädellyt soluväliaineen muutokset sydämen ja aorttaläpän rakenteessa. Soluväliaineen rakenteen muodostavien kollageenien ja elastiinin lisäksi soluväliaineessa on rakenteeseen kuulumattomia proteiineja. Tässä väitöskirjassa tutkittiin sidekudoksen kertymiseen ja kudosten kalkkiutumiseen osallistuvia soluväliaineen proteiineja sydämen vajaatoiminnassa sekä aorttastenoosiin johtavassa kalkkiuttavassa aorttaläppäviassa. Tutkimuksessa selvitettiin sydämen soluväliaineen proteiinien ilmentymistä painekuormituksen, sydäninfarktin ja pitkäaikaisen munuaisten vajaatoiminnan koemalleissa rotalla. Tutkittavia proteiineja olivat luun morfogeneettiset proteiinit 2 ja 4, luun sialoproteiini, matriksin Gla proteiini (MGP), osteoaktiviini, osteopontiini, periostiini ja pleiotropiini. Edellä mainittujen proteiinien lisäksi osteoprotegeriinin ja trombospondiinien 1-4 ilmentymistä tutkittiin kalkkiuttavan aorttaläppävian eri kehitysvaiheissa. Aorttaläpät oli kerätty tekoläppäleikkauspotilailta. Sydämessä MGP:n ilmentyminen lisääntyi kaikissa muissa paitsi munuaisten vajaatoiminnan koemallissa. Angiotensiini II nosti MGP:n ilmentymistä sydänlihassoluissa ja sidekudossoluissa. Periostiinin ilmentyminen lisääntyi sydämen uudelleenmuovautumisessa, muttei aorttaläppäviassa. Lisäksi munuaisten vajaatoiminnan aiheuttama periostiinin ilmentymisen muutos sydämessä liittyi sekä sydämen kasvuun, verenpaineen nousuun että muiden sidekudosta muokkaavien proteiinien ilmentymiseen. Luun sialoproteiinin ja osteopontiinin ilmentymiset erosivat toisistaan erilaisissa sydämen vajaatoiminnan malleissa, mutta aorttaläpissä niiden molempien ilmentyminen oli suhteessa läpän kalkkiutumiseen. Osteoprotegeriinin geenin ilmentyminen lisääntyi kalkkiutuneissa aorttaläpissä vaikkakin proteiinin määrä pysyi vähäisenä. Luun morfogeneettisten proteiinien ilmentyminen oli alentunut sairaissa läpissä, muttei sydämessä munuaisten vajaatoiminnan aikana. Aorttaläpissä ilmennettiin kaikkia trombospondiineita, joista trombospondiini-2:n ilmentyminen kasvoi sairaissa aorttaläpissä. Kalkkiutuneissa läpissä solunsisäinen Akt/NF-κB–signaalinvälitysjärjestelmä oli vaimentunut. Tutkimus osoittaa, että soluväliaineen proteiinien ilmentymistä säädellään eri tavoin sydämen vajaatoiminnassa ja aorttastenoosissa kudoksen uudelleenmuovautumisprosessin aikana
26
Tate, Ciara Caltagirone. "The role of extracellular matrix proteins in traumatic brain injury and cell transplantation". Diss., Available online, Georgia Institute of Technology, 2006, 2006. http://etd.gatech.edu/theses/available/etd-05302006-203440/.
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Thesis (Ph. D.)--Biomedical Engineering, Georgia Institute of Technology, 2007.Bellamkonda, Ravi, Committee Member ; LaPlaca, Michelle, Committee Chair ; Stein, Donald, Committee Member ; Garca̕, Andrš, Committee Member ; Archer, David, Committee Member ; Borlongan, Cesario, Committee Member.
27
McVey, Gillian. "The expression, purification and characterisation of hyaluronan-binding domains from extracellular matrix proteins". Thesis, University of Oxford, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.270208.
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Stone, Louise Catherine. "Regulation of hepatic stellate cell phenotype and cytoglobin expression by extracellular matrix proteins". Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5680/.
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All chronic liver diseases can induce fibrosis and lead to liver cirrhosis. Within liver disease, hepatic stellate cells (HSC) are accepted as the major effectors of fibrogenesis and changes in the extracellular matrix (ECM). Cytoglobin (CYGB), a hexacoordinated globin, is upregulated in liver disease, and expression has been reported to be specific to HSCs in the liver, though this is disputed. Data presented in Chapter 3 of this thesis confirm upregulation of Cygb in murine models of liver disease and diseased human liver tissue. Chapter 4 shows how ECM can effect HSC morphology, behaviour and phenotype with collagen I, an important component of the hepatic scar conferring an activated HSC phenotype, and laminin, a basal protein in a normal liver, inducing a more quiescent phenotype in HSC cell lines HSC-T6 and LX-2. Chapter 5 demonstrates the novel observation of collagen I-induced downregulation, and laminin-induced upregulation, of Cygb in HSC-T6s. Chapter 6 explores the role of cell signalling through membrane receptors and regulation of Cygb expression, identifying phosphorylated focal adhesion kinase as a mechanism of signal transduction through integrin activation. These findings suggest that Cygb expression is modulated by ‘outside-in signalling’ and this is important in the activation status of HSCs.
29
Ip, Ying-chi. "MT1-MMP in relation to metastasis of hepatocellular carcinoma". Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31490189.
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Wu, Wing-kei Ricky. "Development of an in vitro assay for MMP cleavage /". View the Table of Contents & Abstract, 2005. http://sunzi.lib.hku.hk/hkuto/record/B31494183.
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Thoumine, Olivier. "Effect of steady and pulsatile laminar shear stress on extracellular matrix and focal contact-associated proteins of endothelial cells". Diss., Georgia Institute of Technology, 1994. http://hdl.handle.net/1853/17079.
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Wu, Wing-kei Ricky, e 胡永基. "Development of an in vitro assay for MMP cleavage". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B4501050X.
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Xu, Jinye, e 徐金叶. "Two-photon photochemical crosslinking-based fabrication of protein microstructures". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B47179223.
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One of the challenges in tissue engineering is to fabricate scaffolds which can mimic the natural microenvironments of cells. In a cell niche, biophysical and mechanical cues are crucial factors influencing cell functions. Given the complexity of natural extracellular matrix (ECM) engineered ECMs providing controllable biophysical and mechanical cues are appealing both in enhancing the understanding of cell-matrix interaction and in controlling cell fates in vitro.
The ultimate goal of our study is to establish a platform as an engineered ECM by fabricating customized solid protein microstructures from solution using two-photon photochemical crosslinking, a novel laser-based freeform fabrication technique.
In this study, protein structures varying from submicron lines, 2D micropatterns and microporous matrices, to 3D micropillars were successfully fabricated, demonstrating freeform fabrication capability with two-photon photochemical crosslinking.
Two-photon fluorescent imaging and scanning electron microscope (SEM)-based microstructural characterization revealed that power, scan speed, total exposure time and concentrations of protein (bovine serum albumin) and photosensitizer (rose Bengal) in the solution were crucial processing parameters in this fabrication technique. Quantitative imaging analysis showed that porosity of protein matrices was highly dependent on processing parameters including power, scan speed, number of cycles in time series scan and protein concentrations in the solution.
An atomic force microscopy (AFM)-based step change nano-compression test was used to measure the reduced elastic modulus of 3D viscoelastic protein micro-pillars fabricated, as a pilot study.
Microporous protein matrices and 3D micropillar arrays fabricated with two-photon photochemical crosslinking can be used as engineered ECM for future study in cell-ECM interactions.published_or_final_version
Mechanical Engineering
Master
Master of Philosophy
34
Ma, Jiaoni, e 馬姣妮. "Multiphoton based biofabrication of 3D protein micro-structures and micro-patterns : voxel and cell matrix niche studies". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208048.
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Brown, Ashley Carson. "Modulation of pulmonary epithelial to mesenchymal transitions through control of extracellular matrix microenvironments". Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/44827.
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Epithelial to mesenchymal transition (EMT), the transdifferentation of an epithelial cell into a mesenchymal fibroblast, is a cellular process necessary for embryonic development and wound healing. However, uncontrolled EMT can result in accumulation of myofibroblasts and excessive deposition of ECM, contributing to the pathological progression of fibrotic diseases such as pulmonary fibrosis. The ability to control EMT is important for development of novel therapeutics for fibrotic pathologies and for designing novel biomaterials for tissue engineering applications seeking to promote EMT for development of complex tissues. EMT is a highly orchestrated process involving the integration of biochemical signals from specific integrin-mediated interactions with extracellular matrix (ECM) proteins and soluble growth factors such as TGFβ. TGFβ, a potent inducer of EMT, is activated via cell contraction-mediated mechanical release of the growth factor from a macromolecular latency complex. Thus TGFβ activity and subsequent EMT may be influenced by the biochemical and biophysical state of the surrounding ECM. Based on these knowns, it was hypothesized that both changes in integrin engagement and increases in substrate rigidity would modulate EMT due to changes in epithelial cell contraction and TGFβ activation. Here we show that integrin-specific interactions with fibronectin (Fn) fragments displaying both the RGD and PHSRN binding sites facilitate cell binding through α5β1 and α3β1 integrins, and lead to maintenance of epithelial phenotype, while Fn fragments displaying only the RGD site facilitate cell binding through αv integrins and lead to EMT. An in depth investigation into α3β1 binding to Fn fragments indicates that binding is dependent on both the presence and orientation of the PHSRN site. Studies investigating the contribution of ECM stiffening on EMT responses show that increasingly rigid Fn substrates are sufficient to induce spontaneous EMT. Analysis of TGFβ-responsive genes implicate TGFβ-expression, activation or signaling as a mechanism for the observed EMT responses. Together these results suggest that the ECM micromechanical environment is a significant contributor to the onset of EMT responses and provide insights into the design of biomaterial-based microenvironments for the control of epithelial cell phenotype.
36
McGuire, Vincent Michael. "Assembly and function of the PsB multiprotein complex during spore differentiation in Dictyostelium discoideum /". free to MU campus, to others for purchase, 1996. http://wwwlib.umi.com/cr/mo/fullcit?p9737858.
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Cardó, i. Vila Marina. "Functional role of extracellular matrix proteins and their receptors in apoptosis and cell survival". Doctoral thesis, Universitat de Barcelona, 2003. http://hdl.handle.net/10803/3009.
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Macrophages require presence of M-CSF to survive and proliferate. Incubation of bone marrow macrophages with soluble factors (LPS or IFN-gamma) or insoluble factors such as extracellular matrix proteins (Decorin, FN) macrophage proliferation was blocked. Moreover, pretreatment of macrophages with IFN-gamma protects from apoptosis induced by several stimuli. Inhibition of p21Waf with antisense oligonucleotides or using null mice showed that the induction of p21Waf by IFN-gamma mediate this protection. Thus, IFN-gamma makes macrophages unresponsive to apoptotic stimuli by inducing p21Waf and arresting the cell cycle at the G1/S boundary. The insoluble factors, decorin and fibronectin, inhibit macrophage proliferation through p27kip1 expression and the modification of ERK activity. Decorin treated macrophages but not fibronectin protect from apoptosis mechanism that require p21Waf expression. Decorin enhances the IFNgamma-induced expression of IA-alpha and IAß MHC class II genes. Moreover, it increases the IFN-gamma or LPS-induced expression of inducible NO synthase, TNF-alpha, IL-1ß, and IL-6 genes and the secretion of these cytokines. Using a number of extracellular matrix proteins, we found a negative correlation between adhesion and proliferation. However, the effect of decorin on macrophage activation is explained by its ability to block the binding of autocrine-produced TGFß on the surface of macrophages.
These soluble and insoluble factors modulate the cell response through the interaction with surface receptors. Cell surface receptors of the integrin family are important regulators of the cell behavior. ß5 cytoplasmic domain has been reported to control cell migration and proliferation. Certain postadhesion are regulated through a pathway that requires both avß5 and PKC activity.
Extensive data have been reported on the use of phage libraries to identify ligands. The large molecular diversity represented in phage peptide libraries facilitates the identification of motifs that map to protein interaction sites. Here we introduced an approach based on phage display technology to identify molecules that specifically interact with the cytoplasmic of the ß5 integrin subunit. We showed that a peptide that mimics annexin V binds to the cytoplasmic domain and triggers apoptosis. Annexin V is a cytosolic signaling protein known to inhibit PKC activity, and we demonstrated that annexin-V only binds to active form of PKC. Induction of apoptosis by this peptide is modulated by growth factors and by PKC antagonist. Caspase activity and the expression of ß5 integrin are also required.
Caspases play an important role on apoptosis. XIAP functions as a caspase inhibitor and is a member of the inhibitors of apoptosis (IAP) family of proteins. All of the members of the IAP have been shown to inhibit programmed cell death. The human IAP family members bind to caspase 3 and caspase 7 with inhibitory constant values. We have selected peptides from a phage display library by using recombinant full-length human XIAP. A consensus motif was recovered from two independent screenings by using different libraries. Phage displaying variations of the consensus sequence bound specifically to the BIR2 domain of XIAP but not to other IAPs. Protein-protein interaction assays revealed that caspase-3 and -7 blocked the binding of the XIAP-binding phage to XIAP, indicating that this peptide targets a domain within XIAP that is related to the caspase-binding site. We also demonstrated that an internalizing version of the XIAP-binding peptide identified in our screenings could induce apoptosis in leukemia cells.
Using a new approach for the screening by phage display technology we also characterize cells surface receptors in endothelial cell activation and proliferation. The molecular diversity in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. These data represents a step toward the construction of a molecular map of human vasculature and may have broad implications for development of targeted therapies.
38
Nievergelt, Alexandra. "Regulation of HT1080 fibrosarcoma cell migration : role of signalling pathways and extracellular matrix proteins /". [S.l.] : [s.n.], 2004. http://www.zb.unibe.ch/download/eldiss/04nievergelt_a.pdf.
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Da, Silva Lodge Michelle. "Extracellular matrix associated proteins and processing enzymes as urinary biomarkers of Chronic Kidney Disease". Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/11490/.
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Background: Chronic Kidney Disease (CKD) is often progressive leading to End Stage Renal Disease (ESRD). Early detection of progressive CKD would almost certainly improve long term outcome. Current kidney function tests have serious limitations as they only can detect dysfunction after significant damage has occurred, provide limited help with diagnosis and are unhelpful in assessing early response to therapy or long term prognosis. Therefore there is a requirement for identification of early and reliable non invasive biomarkers of kidney disease and its progression. Regardless of the underlying disease, fibrosis drives movement to ESRD. Fibrosis is characterised by excessive accumulation of Extracellular Matrix (ECM). This thesis tests the hypothesis that mediators of the kidney fibrotic process are present in urine and would make good biomarkers of CKD and its progression. Aims: To assess urine samples from three animal models of kidney fibrosis (5/6th Subtotalnephrectomy (SNx), Diabetic Nephropathy (DN) and Chronic Allograph Nephropathy (CAN) as well as 325 human urine samples (292 CKD and 33 controls) to determine if urinary ECM molecules, Transglutaminase 2 (TG2), ε (γ-glutamyl) lysine, Hydroxyproline, Metalloproteinases 1, 2 and 9, TIMPs 1, 2 and 3, TIMP-1/MMP-1 complex, PAI-1 and MMP activity have potential to act as an early biomarker of kidney scarring and if any of them could predict the rate of progression better than Albuminuria. Experimental methods: Cation exchange chromatography was used to evaluate urine levels of ε (γ-glutamyl) lysine and Hydroxyproline. An in-house developed sandwich ELISA was used to analyse urine and blood levels of TG2 and commercially available immunoassays were used for determination of urine concentration of MMPs 1, 2 and 9, TIMPs 1, 2 and 3, TIMP-1/MMP-1 complex and PAI-1. MMP activity was measured by the EnzCheck Collagenase assay. One way ANOVA with Bonferroni correction was applied to estimate differences between groups. Area under the curve for Receiver Operating Characteristic (ROC) analysis was used to determine prediction accuracy. p < 0.05 was considered statistically significant. Results: TG2 and ε (γ-glutamyl) lysine excretion were significantly increased as renal scarring developed in SNx and CAN models. However, in DN, increased levels were only observed as a 24 hour excretion at 8 months of study only due to the increased proteinuric state. TG inhibitor treated animals had a reduction in the measured levels of both TG2 and of ε (γ-glutamyl) lysine in the SNx study. Urine Hydroxyproline had increased levels as renal disease scarring progressed. MMP-1 was significantly increased in SNx and DN animals, with MMP-9 excretion undetectable in all control samples. Amongst the TIMPs, TIMP-1 gave the most promising response in the early stages of SNx and DN with a 6.4 fold increase at 7 days post SNx, p-0.0025 and 25 fold increase at 4 months post STZ injection, p=0.0006. Whereas in CAN, the TIMP2: CR ratio was double that in F-L Allografts than in L-L Isografts (p=0.0095) as early as 8 weeks post-transplant and remained elevated up to 33 weeks. Urine PAI-1 excretion was within the lower limits of detection and therefore was not used in human samples. In the human study, ROC curve analysis demonstrated that the TG2/CR ratio (86.4%) and TIMP1/CR ratio (75.7%) are better predictors of patients with progressive CKD than ACR (73.5%) indicating their potential as non-invasive biomarkers of progressive kidney scarring. The ROC curve analysis of ε (γ-glutamyl) lysine/CR ratio (73.3%) and TIMP2/ CR ratio (71.2%) presented similar levels of accuracy of prediction as ACR, whereas all other candidates were inferior to ACR. Measurement of MMP-1 activity had a remarkable predictive value in detecting rapid progressive patients, as very low levels were found in this subgroup of patients. A combo ROC curve analysis using TG2CR, XLCR, TIMP1CR and ACR as prognostic tools of CKD progression generated a remarkable 87.7% risk prediction. Conclusions: The data presented in this thesis demonstrates a potential benefit of using ECM molecules (especially TG2, TIMP-1 and ε (γ-glutamyl) lysine) detected in urine as biomarkers of CKD progression. Using a combined biomarker panel containing ACR, TG2/CR, TIMP/CR and XL/CR ratios may allow the earlier and more reliable detection of patients with more aggressive CKD that requires stronger treatment strategies to give better long term outcomes and facilitate shorter clinical trials in CKD.
40
Leung, Wai-lun Alan. "Functional analyses of type IIA procollagen in embryo development /". View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36434188.
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Ferron, Florence Joelle. "The implications of fibulin-5 on elastin assembly and its role in the elastic fiber /". Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101846.
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The extracellular matrix (ECM) is the material found surrounding the cells in a tissue. One component of the ECM is the elastic fiber, which confers the property of elasticity to its environment. Organs such as the lung, skin and major blood vessels have an abundance of elastic fibers so that they are able to expand and recoil. Elastic fibers are composed of two main components; elastin and microfibrils. Microfibrils are composed primarily of fibrillin-1 and provide a scaffold unto which tropoelastin monomers assemble. Elastic fibers interact with many other proteins in the ECM, one of which is fibulin-5. Based on the severe elastic fiber defects observed in the fibulin-5 null mouse, it was established that fibulin-5 plays an essential role in elastic fiber development. This role may be in the deposition of tropoelastin onto microfibrils and/or in stabilizing the elastic fibers in the extracellular matrix. In the present study, the relationship between fibulin-5 and the elastic fiber was investigated through a number of in vivo and in vitro experiments. To test the hypothesis that fibulin-5 requires the presence of elastin to assemble in the ECM, full-length recombinant fibulin-5 (rF5) was purified from transfected cells and used to make a fibulin-5 antibody. Solid-phase binding assays using rF5 showed that fibulin-5 binds tropoelastin at two sites; the initial portion of the C-terminus and the first calcium-binding epidermal growth factor-like domain at the N-terminus. Immunofluorescence staining of elastin null mouse embryonic fibroblast cultures revealed that fibulin-5 does not require elastin to be present in the ECM in order to assemble. Subsequently, solid-phase binding assays showed that fibulin-5 can bind to the N-terminus of fibrillin-1. To determine if fibulin-5 could exist independent of elastin and/or fibrillin-1 in vivo, an immunohistochemical analysis was conducted on heart, liver, lung, colon, spleen, testis and kidney. All three proteins were co-localized in all organs except in the kidney, where fibrillin-1 was found to independently stain the capillary tufts of the renal corpuscles and renal tubules. Thus, fibulin-5 may be co-regulated with elastin and is not present on elastin-independent microfibrils. Additionally, novel locations of elastic fibers were uncovered in the heart, liver, colon, spleen and testis. Overall, this study provides important insights as to the role of fibulin-5 in elastic fiber structure and assembly and also reveals the complexity in understanding the pathogenesis of diseases involving elastic fiber proteins.
42
Ip, Ying-chi, e 葉瑩芝. "MT1-MMP in relation to metastasis of hepatocellular carcinoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31490189.
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Sun, Wentao, e 孙文韬. "The effects of Panax notoginseng extracts and its components on TNF-alpha induced MMP-9 expression and activity". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/207686.
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Matrix metalloproteinase (MMP) induced extra cellular matrix (ECM) degradation is a crucial process involved in the development of many chronic inflammatory diseases, including cardiac remodeling and cancer metastasis. In cardiac remodeling, the presence of pathological stimuli leads to elevated MMP-9 expression and impairment of cardiac performance, which subsequently develops into heart failure. While in tumorgenesis, MMP-9 has been found to play key roles in metastasis, as it can break physical barriers for the tumor. Therefore, searching for agents targeting MMP-9 is a new direction for the treatment of cardiac remodeling and cancer metastasis.
Chinese herbal medicine is becoming increasingly used worldwide in recent decades. In the past twenty years, as many highly selective and sensitive bioassays were introduced into the bioactive compounds screening from herbal medicine, more than one hundred new drug candidates have been identified. Therefore, herbal medicine is a potential source of bioactive compounds. Panax notoginseng (PNG) is one of the most common traditional Chinese medicines to treat cardiovascular diseases, and it was also reported to have anti-cancer effect. We hypothesized that it contains bioactive compounds that could inhibit MMP-9 activity in cardiomyocytes and cancer cells.
In order to examine the effect of PNG on cardiac remodeling and cancer metastasis, we employed TNF-α induced MMP-9 in H9c2 cell (a rat cardiomyocyte) and HepG-2 cell (a human hepatoma cell) as an in vitro assay, respectively. PNG was first extracted by four different extraction methods according to the polarity of the solvent. The most effective fraction in suppressing MMP-9 activity in TNF-α induced H9c2 cell was chosen for further separation by silica gel column chromatography and high performance liquid chromatography (HPLC) until a single compound was isolated. According to the result of spectroscopic analysis by NMR, the compound was identified as ginsenoside Rb1. For the bioactivity assays, real-time quantitative polymerase chain reaction (QPCR) and Enzyme-linked immunosorbent assay (ELISA) were used to measure the mRNA and protein expression of MMP-9, respectively. We also examined the MMP-9 activity by gelatin zymography. The results showed that both of the PNG extract obtained from 10% ethanol extraction method (PNG-3) and purified Compound P (ginsenoside Rb1) showed significant inhibitory effect on MMP-9 expression and activity in H9c2 cells and HepG-2 cells.
We further examined the molecular mechanisms of the inhibitory effect of PNG-3. H9c2 and HepG-2 cells were pretreated with different kinase inhibitors followed by the activation by TNF-α. The results showed the protein kinase R (PKR) inhibitor could inhibit TNF-α induced MMP-9 in both of the two cell lines. Furthermore, the results of Western blot showed the PNG-3 suppressed the phosphorylation of eIF-2α which is a down-stream effector of PKR in TNF-α stimulated H9c2 and HepG-2 cells, respectively. Therefore, PNG-3 may act through PKR to regulate TNF-α induced MMP-9 activity.
In summary, bioactivity guided fractionation is an effective way of isolating bioactive compounds from medicinal herbs. In addition, PNG containing ginsenoside Rb1 may be a potential candidate of MMP-9 inhibition for the treatment of cardiac remodeling and cancer metastasis.published_or_final_version
Paediatrics and Adolescent Medicine
Master
Master of Philosophy
44
Petersson, Ulrika. "Studies on three matrix molecules in bone and dentin /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-702-9/.
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Liao, Zhiming. "Molecular aspects of cardiac cytochrome C oxidase and extracellular matrix proteins in copper-deficient rats /". The Ohio State University, 1994. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487853913100837.
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Heilshorn, Sarah Christine Tirrell David A. "Design and characterization of artificial extracellular matrix proteins for use as small-diameter vascular grafts /". Diss., Pasadena, Calif. : California Institute of Technology, 2004. http://resolver.caltech.edu/CaltechETD:etd-05242004-103633.
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Shelton, Setareh Lillian. "Characterization of mechanisms regulating scleral extracellular matrix remodeling to promote myopia development". Oklahoma City : [s.n.], 2009.
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Lavoie, Jean-Michel. "Mammalian cell culture on poly (dimethyl siloxane) functionalized for covalent immobilization of extracellular matrix-derived proteins". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116017.
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In vitro cell culture is an essential part of many cell and tissue engineering approaches. In particular, monolayer culture of mammalian cells is a key tool for applications such as cell therapy. Novel bioreactors like the Cellerator(TM) allow for expansion of cell populations on mechanically stimulated surfaces coated with proteins. This thesis constitutes a preliminary study which focused on cell-matrix interactions in the absence of stretch. The aim was to establish standard protocols for protein coating on poly (dimethyl siloxane) (PDMS) and for measuring cell proliferation. Specifically, the proliferation of rat pulmonary artery vascular smooth muscle (PAC1) cells on type I collagen and soluble fibronectin was studied. Growth curves were obtained and the doubling time for subconfluent cultures was computed. Although cell-matrix interactions do not enhance proliferation of PAC1 cells, it was found that a preliminary sulphuric acid treatment is necessary to yield a well-behaved culture.
49
Phillips, Jonathan Adam. "Convergent Biochemical and Biomechanical Pathways in Tissue Remodeling: The Role of α₂β₁ Integrin and MMP Activity: A Dissertation". eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/274.
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The extracellular matrix is a multi-functional environment that cells inhabit to form living tissue. To maintain the tissue, cells require constant telemetry with the matrix and respond to a variety of cues by remodeling matrix architecture. In this study the physical and biochemical manipulation of the matrix by resident cells is explored to better understand how these are used to remodel tissue.
Cell-populated collagen hydrogels are used as a controllable in vitro tissue model. To directly measure mechanical forces involved with gel contraction, a culture force monitor was designed and built. Measuring dimensional changes together with contractile forces presents a method of separating mechanisms that influence tissue remodeling.
Together, these techniques revealed a correlation between contractile force and gel deformation, suggesting a novel method for examining the material properties of the matrix. Limiting matrix metalloproteinase (MMP) activity altered the correlation as predicted, indicating a stiffer matrix.
Contractile force was found to be regulated independent of MMP activity. In contrast, contractile force was found to be dependent on α2β1 integrin function. Collagen gel contraction correlated with both α2β1 function and MMP activity, and was significantly enhanced when combined.
The results of this study indicate cells have the capacity to use multiple mechanisms for remodeling the extracellular matrix and may alternately use them together or independently to vary the rate of matrix contraction.
50
Ojaniemi, M. (Marja). "Docking proteins p130Cas and p120Cbl in integrin and growth factor receptor signalling". Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:9514253078.
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Abstract
Adhesive interactions between cells and extracellular matrix
proteins play a vital role in biological processes such as cell
proliferation, differentiation and survival. Integrins comprise
a major family of cell surface receptors that mediate these interactions.
Integrin engagement triggers adhesion-dependent intracellular signalling
cascades that include the phosphorylation of tyrosines in intracellular
signalling proteins. Integrin-dependent signals act in concert
with signals from growth factors and other signalling receptors.
The objective of this thesis was to study how cell adhesion and growth
factors interact with intracellular components to regulate cell
behavior in normal and transformed cells.
One of the main proteins phosphorylated following integrin
ligation in several different cell types is the docking protein
p130Cas (Cas), which is tyrosine phosphorylated
after stimulation of cells with low concentrations of epidermal
growth factor (EGF). Tyrosine-phosphorylated Cas associates with
an adapter protein c-Crk, the main binding protein for Cas, suggesting
a novel role for EGF in Cas signalling. The interaction of cells
with a variety of agonists such as growth factors and integrin ligation
results in stimulation of mitogen-activated protein kinases (MAPKs),
which control the expression of genes important for many cell functions.
Expression of Cas and Crk induces activation of C-Jun N-terminal
kinases (JNKs), which are members of MAPK family. JNK activation
induced by integrin ligand binding is blocked by the expression
of a dominant-negative mutant of Cas or Crk demonstrating an important
role for the Cas-Crk complex in integrin-mediated JNK activation.
The proto-oncogene product p120Cbl (Cbl)
was identified as the main tyrosine-phosphorylated protein following
integrin ligation in hematopoietic cells of myeloid lineage. Tyrosine-phosphorylated
Cbl interacts with and activates other signalling proteins, such
as Src tyrosine kinase and phosphatidylinositol 3"-kinase
(PI 3-kinase), thereby mediating adhesion-dependent signals in hematopoietic
cells. Unlike the cellular Cbl, the transforming mutants of Cbl
were tyrosine-phosphorylated in an adhesion-independent manner
and interacted with and activated signalling molecules both in
suspended and in adherent cells. Further, the oncogenic forms of
Cbl induced anchorage-independent but serum-dependent proliferation
of cells. These results support the view that transformation by
Cbl results from constitutive activation of integrin-dependent
rather than growth factor-dependent signalling events.