Endothelial cell integrin alpha 5 beta 1 expression is modulated by cytokines and during migration in vitro

Alterations in endothelial cell-extracellular matrix interactions are centr al to the process of angiogenesis. We have investigated the effect of wound -induced two-dimensional migration, basic fibroblast growth factor (bFGF), transforming growth factor-beta 1 (TGF-beta 1) and leukemia inhibitory fact or (LIF) on expression of the alpha(5)beta(1) integrin in endothelial cells . In multiple-wounded monolayers of bovine microvascular endothelial (BME) cells, an increase in mRNA and total protein for both alpha(5) and beta(1) subunits was observed, and this could be correlated with a reduction in cel l density but not proliferation, both of which are induced following woundi ng. Although as previously reported, the as subunit was increased when cell s were exposed to TGF-beta 1 alone, co-addition of bFGF and TGF-beta 1 resu lted in a striking synergistic induction of alpha 5, with no significant ch anges in the expression of beta 1, In contrast, the alpha 5 subunit was dec reased by LIF in bovine aortic endothelial but not in BME cells. These find ings suggest that quantitative alterations in alpha 5 and beta 1 integrin s ubunit expression modulate the adhesive and migratory properties of endothe lial cells during angiogenesis.