Integrin-linked kinase controls vascular wall formation by negatively regulating Rho/ROCK-mediated vascular smooth muscle cell contraction

Genes Dev. 2009 Oct 1;23(19):2278-83. doi: 10.1101/gad.535409.

Abstract

Vascular smooth muscle cells (VSMCs) form contractile layers around larger blood vessels in a process that is essential for the formation of a fully functional vasculature. Here, we show that integrin-linked kinase (ILK) is required for the formation of a unitary layer of aligned VSMCs around arterioles and the regulation of blood vessel constriction in mice. In the absence of ILK, activated Rho/ROCK signaling induces the elevated phosphorylation of myosin light chain leading to abnormally enhanced VSMC contraction in vitro and in vivo. Our findings identify ILK as a key component regulating vascular wall formation by negatively modulating VSMC contractility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Cell Proliferation
  • Cells, Cultured
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / embryology*
  • Muscle, Smooth, Vascular / metabolism
  • Myosin Light Chains / metabolism
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • rho-Associated Kinases / metabolism*

Substances

  • Myosin Light Chains
  • integrin-linked kinase
  • Protein Serine-Threonine Kinases
  • rho-Associated Kinases