Differences in the regulation of fibroblast contraction of floating versusstressed collagen matrices

To learn more about the regulation of contraction of collagen matrices by f ibroblasts, we compared the ability of lysophosphatidic: acid (LPA) and pla telet-derived growth factor (PDGF) to stimulate contraction of floating and stressed collagen matrices. In floating collagen matrices, PDGF and LPA st imulated contraction with similar kinetics, but appeared to utilize complem entary signaling pathways since contraction obtained by the combination of growth factors exceeded that observed with saturating concentrations of eit her alone. The PDGF-simulated pathway was selectively inhibited by the prot ein kinase inhibitor KT5926. In stressed collagen matrices, PDGF and LPA st imulated contraction with different kinetics, with LPA acting rapidly and P DGF acting only after an similar to 1-h lag period. Pertussis toxin, known to block signaling through the Gi class of heterotrimeric G-proteins, inhib ited LPA-stimulated contraction of floating but not stressed matrices, sugg esting that LPA-stimulated contraction depends on receptors coupled to diff erent G-proteins in floating and stressed matrices. On the other hand, the Rho inhibitor C3 exotransferase blocked contraction of both floating and st ressed collagen matrices. These results suggest the possibility that distin ct signaling mechanisms regulate contraction of floating and stressed colla gen matrices.