TGF-beta 1 reverses PDGF-stimulated migration of human aortic smooth muscle cells in vitro

Abstract

Platelet-derived growth factor (PDGF) and transforming growth factor beta-1(TGF-beta 1) were tested separately or together for the ability to stimulate migration of human aortic vascular smooth muscle cells (VSMC). PDGF (10 ng/ml) stimulated migration of VSMC over a 48-h period. TGF-beta 1 (10 ng/ml) had no effect on migration during the same period. VSMC exposed simultaneously to both TGF-beta 1 and PDGF exhibited diminished migration (50%) when compared to cells treated only with PDGF. Cells that migrated in the presence of PDGF possessed short actin cables that extended from cellular processes at the leading edge of migrating cells; focal adhesions containing the alpha v beta 3/beta 5 integrins localised to the same region. Cells grown in the presence of TGF-beta 1 exhibited long, intensely stained actin filaments that spanned the entire length of the cell and were similar to untreated control VSMC. Focal adhesions containing alpha v beta 3/beta 5 distributed evenly on the basal surface in both TGF-beta 1-treated cells and control cultures. Cellular responses to PDGF were mitigated when TGF-beta 1 was present in the culture medium. VSMC grown in the presence of both PDGF and TGF-beta 1 exhibited elongated actin filaments that were similar to nonmotile TGF-beta 1-treated cultures. Concomitant exposure of VSMC to PDGF and TGF-beta 1 resulted in focal adhesions that distributed evenly on the lower cell surface. This study suggests that TGF-beta 1 can partially reverse the stimulatory effect of PDGF on VSMC migration in vitro by modifying the actin cytoskeleton and the distribution of the alpha v beta3/beta 5 integrins.