Treatment of human fibroblasts with vanadate and platelet-derived growth factor in the presence of serum inhibits collagen matrix contraction.
Human fibroblasts cultured in an anchored collagen matrix reorganize the matrix and develop stress. Upon experimental release of the matrix, cells contract the matrix, a phenomenon that has been studied as an in vitro model of wound contraction. We have found that treatment of fibroblasts in stressed collagen matrices with vanadate and platelet-derived growth factor (PDGF) in serum-containing medium inhibits the ability of cells to contract the matrix. Vanadate/PDGF/serum stimulation did not block contraction immediately, but rather resulted in generation of an inhibitory signal that developed over a period of 80 min. The signal was highly specific since other factors such as lysophosphatidic acid and epidermal growth factor were unable to replace PDGF or serum. The presence of vanadate also blocked dephosphorylation of p-Tyr-PDGF receptors after PDGF/serum stimulation and caused accumulation of tyrosine-phosphorylated proteins in the cells. In parallel experiments, fibroblasts in monolayer culture were found to undergo reorganization of their actin cytoskeleton when treated with vanadate in the presence of PDGF and serum-containing medium. Our results suggest that a p-Tyr signaling pathway is important in the regulation of wound contraction.
Lin
Y C
YC
Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical School, Dallas 75235, USA.
Grinnell
F
F
D000199:Actins / Q000187:drug effects; D001798:Blood Proteins / Q000494:pharmacology*; D002478:Cells, Cultured / Q000502:physiology / Q000648:ultrastructure; D003094:Collagen / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects*; D005347:Fibroblasts / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects; D014638:Vanadates / Q000494:pharmacology*
D000199:Actins; D001798:Blood Proteins; D010982:Platelet-Derived Growth Factor; D014638:Vanadates; D003094:Collagen; D017479:Receptors, Platelet-Derived Growth Factor; D017027:Protein Tyrosine Phosphatases