βig-h3 triggers signaling pathways mediating adhesion and migration of vascular smooth muscle cells through αvβ5 integrin

Adhesion and migration of vascular smooth muscle cells (VSMCs) play an important role in the pathogenesis of atherosclerosis. These processes involve the interaction of VSMCs with extracellular matrix proteins. Here, we investigated integrin isoforms and signaling pathways mediating the adhesion and migration of VSMCs on beta ig-h3, a transforming growth factor (TGF)-beta-inducible extra cellular matrix protein that is elevated in atherosclerotic plaques. Adhesion assays showed that the alpha v beta 5 integrin is a functional receptor for the adhesion of aortic VSMCs to beta ig-h3. An YH18 motif containing amino acids between 563 and 580 of beta ig-h3 was an essential motif for the adhesion and growth of VSMCs. Interaction between the YH18 motif and the alpha v beta 5 integrin was responsible for the migration of VSMCs on beta ig-h3. Inhibitors of phosphatidylinositide 3-kinase, extracellular signal-regulated kinase (ERK), and Src kinase reduced,the adhesion and migration of VSMCs on beta ig-h3. beta ig-h3 triggered phosphorylation and activation of AKT, ERK, focal adhesion kinase, and paxillin mediating the adhesion and migration of VSMCs. Taken together, these results suggest that beta ig-h3 and alpha v beta 5 integrin play a role in the adhesion and migration of VSMCs during the pathogenesis of atherosclerosis.