FIBROBLAST GROWTH FACTOR-II POTENTIATES VASCULAR SMOOTH-MUSCLE CELL-MIGRATION TO PLATELET-DERIVED GROWTH-FACTOR - UP-REGULATION OF ALPHA(2)BETA(1) INTEGRIN AND DISASSEMBLY OF ACTIN-FILAMENTS

Fibroblast growth factor-2 (FGF-2) has been implicated in vascular smo oth muscle cell (SMC) migration, a key process in vascular disease. We demonstrate here that FGF-2 promotes SMC motility by altering beta(1) integrin-mediated interactions with the extracellular matrix (ECM). F GF-2 significantly increased surface expression of alpha(2) beta(1), a lpha(3) beta(1), and alpha(5) beta(1) integrins on human SMCs, as asse ssed by flow cytometry. The greatest increase was for the collagen-bin ding alpha(2) beta(1) integrin. Despite this, FGF-2 did not increase S MC adhesion to type I collagen but instead promoted SMC elongation and SMC motility. The latter was evaluated by using a microchemotaxis cha mber and by digital time-lapse video microscopy. Although FGF-2 was no t chemotactic for human SMCs, cells preincubated with FGF-2 displayed a 3.1-fold increase in migration to the undersurface of porous type I collagen-coated membranes and a 2.1-fold increase in migration speed o n collagen. Furthermore, chemotaxis to platelet-derived growth factor- BB on collagen was significantly greater in SMCs exposed to FGF-2. FGF -2-induced elongation and migration on collagen were inhibited by a bl ocking anti-alpha(2) beta(1) antibody; however, SMC adhesion to collag en was unaffected. SMC migration on fibronectin was also enhanced by F GF-2, although less prominently: migration through porous membranes in creased 1.8-fold, and migration speed increased 1.3-fold, Also, FGF-2 completely disassembled the smooth muscle alpha-actin-containing stres s fiber network contemporaneously with the change in integrin expressi on and cell shape. We conclude that (1) exogenous FGF-2 promotes SMC m igration and potentiates chemotaxis to PDGF-BB; (2) the promigratory e ffect of FGF-2 is especially prominent on type I collagen and is media ted by upregulation of alpha(2) beta(1) integrin; and (3) FGF-2 disass embles actin stress fibers, which may promote differential utilization of alpha(2) beta(1) integrin for motility but not adhesion. This dyna mic SMC-ECM interplay may be an important mechanism by which FGF-2 fac ilitates SMC motility in vivo.