Integrin-linked kinase controls vascular wall formation by negatively regulating Rho/ROCK-mediated vascular smooth muscle cell contraction.
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.
Kogata
Naoko
N
Vascular Development Laboratory, UK London Research Institute, London WC2A 3PX, United Kingdom.
Tribe
Rachel M
RM
Fässler
Reinhard
R
Way
Michael
M
Adams
Ralf H
RH
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000378:metabolism*; D000099200:Scaffold Protein ILK
D018994:Myosin Light Chains; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D000099200:Scaffold Protein ILK