Platelet isoforms of platelet-derived growth factor stimulate fibroblasts to contract collagen matrices.

Abstract

Fibroplasia and angiogenesis are essential components of tissue repair when substantial tissue has been lost at a site of injury. Platelets and monocyte/macrophages accumulate at these sites and release a variety of growth factors that are thought to initiate and sustain the repair. Often the involved tissue contracts, a process that can markedly reduce the amount of fibroplasia and angiogenesis necessary for the reestablishment of organ integrity. Such tissue contraction occurs over hours or days, a much slower time course than the rapid, reversible contraction of muscle tissue. Fibroblasts, which are rich in f-actin bundles, appear to be responsible for wound contraction. However, the signals that stimulate contraction are not known. Using cultured fibroblasts, which are also rich in f-actin bundles, we demonstrate the platelet and monocyte isoforms of platelet-derived growth factor (PDGF; AB and BB) but not PDGF-AA, can stimulate fibroblasts to contract collagen matrix in a time course similar to that of wound contraction. In addition, PDGF appears to be the predominant fibroblast/collagen gel contraction activity released from platelets. Vasoactive agonists known to stimulate smooth and striated muscle contraction do not stimulate fibroblast-driven collagen gel contraction.

Induction of phenotype modifying cytokines by FERMT1 mutations

“…Gel contraction generally depends on cell contraction, cell tractional forces related to cell locomotion, and initial cell elongation and spreading (Dallon and Ehrlich, 2008;Ehrlich, et al, 1989). In accordance with their activated phenotype, fibroblasts of all three KS patients reduced the size of collagen lattices stronger than their normal counterparts, as seen in fibrotic processes (Tse, et al, 2004;Clark, et al, 1989).…”

Small Cytoskeleton-Associated Molecule, Fibroblast Growth Factor Receptor 1 Oncogene Partner 2/Wound Inducible Transcript-3.0 (FGFR1OP2/wit3.0), Facilitates Fibroblast-Driven Wound Closure

“…36 TGF-␤-stimulated collagen gel contraction appears to be primarily mediated by transdifferentation of myofibroblasts and up-regulation of ␣-SMA, 3,37,38 whereas platelet-derived growth factor-stimulated contraction may be contributed by cytoskeleton rearrangement. 39,40 These studies were conducted by using skin fibroblasts.…”

Obesity and abdominal wound healing in rats

“…Among the likely factors involved in changes to the healing process in the obese are stimulation by transforming growth factor beta (TGF-ß1 and TGF-ß2) 29 and the platelet-derived growth factor (PDGF) 30 , fibroblast adhesion to the collagen matrix and the individual links between the collagen chains 31,32 . A number of authors have described excess adipose tissue as inducing the inflammatory process, possibly due to increased pro-inflammatory mediators like alpha tumor necrosis factor (TNF-) and several interleukins 33 .…”