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

Mol Med Rep. 2014 Apr;9(4):1159-64. doi: 10.3892/mmr.2014.1937. Epub 2014 Feb 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Collagen Type I / metabolism
  • Flow Cytometry
  • Integrin beta1 / metabolism*
  • Male
  • Muscle, Smooth, Vascular / cytology*
  • Myocytes, Smooth Muscle / cytology*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Wnt3A Protein / pharmacology*

Substances

  • Collagen Type I
  • Integrin beta1
  • Wnt3A Protein