The role of 1-intergrins in skeletal muscle differentiation and extracellular matrix assembly
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Integrin subunit β1 forms heterodimeric receptors with at least 12 different α-subunits.These integrins are the main cellular receptors for extracellular matrix and they arenecessary for normal development. In this thesis, the effects of lack of integrin subunitβ1 on matrix deposition and on skeletal muscle development were studied.Furthermore, analysis of integrin α2β1 mediated functions in a cell line lacking collagenreceptors were performed.
Fibronectin matrix deposition was studied in a fibroblast line. deficient in integrin subunit β1, and in its β1-transfected subclones. The fibronectin receptor α5β1 stronglypromoted the process of fibronectin polymerization. Integrin αvβ3 was found to takeover this function in the absence of α5β1, but in a less efficient manner.
Myogenesis was studied by comparing the muscle phenotypes generated in wild-type/β1-null chimeric mice and β1-null embryoid bodies with their wild-typecounterparts. Both in vivo and in embryoid bodies in vitro normal myotubes wereformed in the absence of β1 integrins. However, the process was found to be delayedand incomplete in the β1-deficient embryoid bodies; notably, unfused myosin positivecells were accumulated. Further characterization of the β1-deficient mvotubes in vitroshowed that abnormal basement membranes were produced by these cells although laminin was associated with the cell surface. In several other cell types lamininassembly was shown to be mediated by β1 integrins. After introducing β1 integrin into, β1-deficient epithelial cells both fibronectin and laminin polymerization werenormalized.
Integrin α2β1 expressed in the myoblast cell line C2C12 mediated collagenadhesion, collagen gel contraction, and stimulated expression of tenascin-C mRNA. Incontrast to shown for fibroblast, no correlation between mechanical stress and level oftenascin-C mRNA in collagen gels was observed.
Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2000. , 44 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 939
Biochemistry, β1 Integrins, Matrix Deposition, Skeletal Muscle Cell
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject Medical Biochemistry
IdentifiersURN: urn:nbn:se:uu:diva-474ISBN: 91-554-4752-XOAI: oai:DiVA.org:uu-474DiVA: diva2:165618
2000-05-30, Föreläsningssal C103:05, Biomedicinskt Centrum (BMC), Uppsala, Uppsala, 09:15