Referenced in: none

Automatically associated channels: ClC3 , ClC4

Title: Integrin β3 mediates cerebrovascular remodelling through Src/ClC-3 volume-regulated Cl(-) channel signalling pathway.

Authors: Jia-Wei Zeng, Xiao-Guang Wang, Ming-Ming Ma, Xiao-Fei Lv, Jie Liu, Jia-Guo Zhou, Yong-Yuan Guan

Journal, date & volume: Br. J. Pharmacol., 2014 Jul , 171, 3158-70

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24611720

Abstract
Cerebrovascular remodelling is one of the important risk factors of stroke. The underlying mechanisms are unclear. Integrin β3 and volume-regulated ClC-3 Cl(-) channels have recently been implicated as important contributors to vascular cell proliferation. Therefore, we investigated the role of integrin β3 in cerebrovascular remodelling and related Cl(-) signalling pathway.Cl(-) currents were recorded using a patch clamp technique. The expression of integrin β3 in hypertensive animals was examined by Western blot and immunohistochemisty. Immunoprecipitation, cDNA and siRNA transfection were employed to investigate the integrin β3/Src/ClC-3 signalling.Integrin β3 expression was up-regulated in stroke-prone spontaneously hypertensive rats, 2-kidney 2-clip hypertensive rats and angiotensin II-infused hypertensive mice. Integrin β3 expression was positively correlated with medial cross-sectional area and ClC-3 expression in the basilar artery of 2-kidney 2-clip hypertensive rats. Knockdown of integrin β3 inhibited the proliferation of rat basilar vascular smooth muscle cells induced by angiotensin II. Co-immunoprecipitation and immunofluorescence experiments revealed a physical interaction between integrin β3, Src and ClC-3 protein. The integrin β3/Src/ClC-3 signalling pathway was shown to be involved in the activation of volume-regulated chloride channels induced by both hypo-osmotic stress and angiotensin II. Tyrosine 284 within a concensus Src phosphorylation site was the key point for ClC-3 channel activation. ClC-3 knockout significantly attenuated angiotensin II-induced cerebrovascular remodelling.Integrin β3 mediates cerebrovascular remodelling during hypertension via Src/ClC-3 signalling pathway.