THROMBIN STIMULATION OF MATRIX FIBRONECTIN

Trypsin, thrombin, and peptide analogues of the new amino terminus of the proteolyzed thrombin receptor, SFLLRN and SFLLRNPNDKYEPF, stimulat ed embryonic fibroblasts cultured as 3-dimensional tissue-like aggrega tes to elaborate a fibronectin-rich extracellular matrix. Enzymaticall y inactive thrombin and the control peptide FLLRN failed to stimulate matrix production. The induction of cell proliferation correlated with production of the fibronectin matrix. The regions of active cell prol iferation in the fibroblast aggregates co-localized with the matrix an d peptide analogues of the RGD cell-adhesion site of fibronectin rever sibly inhibited the accumulation of the fibronectin matrix and the sti mulation of cell proliferation by SFLLRN. Two different preparations o f the fibronectin matrix stimulated cell proliferation in aggregates c ultured in growth factor-free medium. We suggest that the stimulation of matrix production is a necessary event for mitogenic signaling in m esenchymal tissue. The tight coupling between the matrigenic and mitog enic activities of growth factors was absent in monolayer cultures of chick embryonic fibroblasts since thrombin and trypsin induced prolife ration of monolayer-cultured cells without inducing the production of a fibronectin matrix. (C) 1996 Wiley-Liss, Inc.