Wnt3a activates β1-integrin and regulates migration and adhesion of vascular smooth muscle cells

Abstract

Vascular smooth muscle cells (VSMCs) are known to undergo functional changes that contribute to the pathogenesis of atherosclerosis and restenosis. Wnts are a family of secreted glycoproteins that bind to transmembrane Frizzled receptors and initiate signaling cascades with indispensable roles during cell migration, adhesion, proliferation, and survival. The present study reports that wingless-type MMTV integration site family, member 3a (Wnt3a) activates the canonical Wnt pathway in rat VSMCs by triggering the phosphorylation of β-catenin at position Ser675 and GSK-3β at position Ser9. Phosphorylation of these two proteins increases VSMC migration and adhesion. In a search for the downstream mediators of Wnt3a's effects on VSMC migration and adhesion, Wnt3a treatment was observed to increase integrin-linked kinase (ILK) protein expression. ILK is a serine/threonine protein kinase that is thought to control cell migration and adhesion by regulating the affinity of β1-integrin for the extracellular matrix. Wnt3a treatment of VSMCs also activated β1-integrin without changing the quantity of protein expressed on the cell surface. These results demonstrate that Wnt3a enhances migration and adhesion of VSMCs by activating β1-integrin.