Extracellular matrix contraction by fibroblasts: Peptide promoters and second messengers

Abstract

Cells contracting connective tissue matrices generate tractional forces in tissues. Studies of fibroblast contraction, using collagen gels in an in vitro model, demonstrate that it involves the actin cytoskeleton, specific extracellular matrix receptors and requires stimulation by exogenous promoters. Fibroblast contraction is stimulated by factors released by platelets and potentially secreted within the contracting tissue. Endothelial cells secrete a potent promoter of fibroblast contraction which has been identified as endothelin 1. The pathway through which fibroblast contraction is stimulated appears to require activation of protein kinase C. Tumor cells can also secrete endothelin. These mechanisms may be relevant to tumor progression.

Differences in the Regulation of Fibroblast Contraction of Floating Versus Stressed Collagen Matrices

“…Staurosporine also selectively blocked PDGF-stimulated contraction, but appeared to do so by interfering with PDGF receptor phosphorylation (26). Previous studies demonstrated that serum-stimulated contraction could be blocked by inhibitors of protein kinase C (35,36), proteintyrosine kinase (36 -38), phospholipase C (39), and phosphatidylinositol 3-kinase (38). None of the other inhibitors used previously, however, was found to preferentially inhibit PDGF- versus LPA-stimulated contraction.…”

European Society of Biomechanics S.M. Perren Award 2010: An adaptation mechanism for fibrous tissue to sustained shortening

“…Cytochalasins inhibit matrix contraction by disrupting the actin filament network of the fibroblasts (Bell et al, 1979;Guidry andGrinnell, 1985, 1987). Cycloheximide blocks protein synthesis by cells (Bell et al, 1979;Guidry andGrinnell, 1985, 1987).…”

“…Cycloheximide blocks protein synthesis by cells (Bell et al, 1979;Guidry andGrinnell, 1985, 1987). For comparison, data from the 0.95 and 1.05 stretch groups, cultured for 3 days in complete medium, were adopted from study design (2): 'stretch-dependent adaptation'.…”

Fibroblasts, myofibroblasts, and wound contraction

“…Factors that inhibit matrix contraction include fibroblast growth factor (Finesmith et al, 1990;Dubertret et al, 1991) and interferon 3' (Gillery et al, 1992). In general, the downstream signaling mechanisms by which growth factors regulate matrix contraction are unknown, but protein kinase C probably is involved (Danowski and Harris, 1988;Guidry, 1992),…”