TGF-BETA-1 REVERSES PDGF-STIMULATED MIGRATION OF HUMAN AORTIC SMOOTH-MUSCLE CELLS IN-VITRO

Platelet-derived growth factor (PDGF) and transforming growth factor b eta-1(TGF-beta 1) were tested separately or together for the ability t o stimulate migration of human aortic vascular smooth muscle cells (VS MC). 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 perio d. VSMC exposed simultaneously to both TGF-beta 1 and PDGF exhibited d iminished migration (50%) when compared to cells treated only with PDG F. Cells that migrated in the presence of PDGF possessed shea actin ca bles that extended from cellular processes at the leading edge of migr ating cells; focal adhesions containing the alpha(v) beta(3)/beta(5) i ntegrins localized to the same region. Cells grown in the presence of TGF-beta 1 exhibited long, intensely stained actin filaments that span ned the entire length of the cell and were similar to untreated contro l VSMC. Focal adhesions containing alpha(v) beta(3)/beta(5) distribute d evenly on the basal surface in both TGF-beta 1-treated cells and con trol cultures. Cellular responses to PDGF were mitigated when TGF-beta 1 was present in the culture medium. VSMC grown in the presence of bo th PDGF and TGF-beta 1 exhibited elongated actin filaments that were s imilar to nonmotile TGF-beta 1-treated cultures. Concomitant exposure of VSMC to PDGF and TGF-beta 1 resulted in focal adhesions that distri buted evenly on the lower cell surface. This study suggests that TGF-b eta 1 can partially reverse the stimulatory effect of PDGF on VSMC mig ration in vibro by modifying the actin cytoskeleton and the distributi on of the alpha(v) beta(3)/beta(5) integrins.