当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > Integrin β3 mediates cerebrovascular remodelling through Src/ClC-3 volume-regulated Cl(-) channel signalling pathway.

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

Abstract：

BACKGROUND AND PURPOSE: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. EXPERIMENTAL APPROACH: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. KEY RESULTS: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. CONCLUSIONS AND IMPLICATIONS:Integrin β3 mediates cerebrovascular remodelling during hypertension via Src/ClC-3 signalling pathway.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Zeng JW,Wang XG,Ma MM,Lv XF,Liu J,Zhou JG,Guan YY

doi

10.1111/bph.12654

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

3158-70

issue

13

eissn

0007-1188

issn

1476-5381

journal_volume

171

pub_type

杂志文章

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