INDUCTION OF BETA(1) INTEGRIN SYNTHESIS BY RECOMBINANT PLATELET-DERIVED GROWTH-FACTOR (PDGF-AB) CORRELATES WITH AN ENHANCED MIGRATORY RESPONSE OF HUMAN DERMAL FIBROBLASTS TO VARIOUS EXTRACELLULAR-MATRIX PROTEINS

Cell migration plays a major role during wound healing and is tightly controlled by a variety of growth factors and extracellular matrix pro teins, The experiments reported here have been designed to study wheth er defined beta(1) integrins are involved in the platelet-derived grow th-factor-AB (PDGF-AB)-modulated migratory response to collagen type I and to fibronectin. Preincubation of fibroblasts with PDGF-AB resulte d in an up to 2.5-fold increase in the migratory response to collagen type I as well as fibronectin and to enhanced synthesis and cell surfa ce expression of the alpha(2), alpha(3), alpha(5), and beta(1) integri n subunits. Function-blocking monoclonal antibodies against the common beta(1) integrin subunit dose-dependently inhibited the PDGF-AB-augme nted migration of fibroblasts to collagen type I and fibronectin, The PDGF-AB-induced migration to collagen type I was also inhibited by ant ibodies against the alpha(2) integrin subunit, whereas the correspondi ng migration to fibronectin was almost completely blocked by the combi ned application of antibodies against the alpha(3) and the alpha(5) in tegrin subunits. Taken together, up-regulation of integrin synthesis a nd expression by human recombinant PDGF-AB correlate with an increase in the migratory response of dermal human fibroblasts to various extra cellular matrix proteins and thus may contribute to an efficient regul ation of cell. migration during wound healing and tissue repair. (C) 1 995 Academic Press, Inc.