| First Author | Zeng JW | Year | 2014 |
| Journal | Br J Pharmacol | Volume | 171 |
| Issue | 13 | Pages | 3158-70 |
| PubMed ID | 24611720 | Mgi Jnum | J:318213 |
| Mgi Id | MGI:6858794 | Doi | 10.1111/bph.12654 |
| Citation | Zeng JW, et al. (2014) Integrin beta3 mediates cerebrovascular remodelling through Src/ClC-3 volume-regulated Cl(-) channel signalling pathway. Br J Pharmacol 171(13):3158-70 |
| abstractText | BACKGROUND AND PURPOSE: Cerebrovascular remodelling is one of the important risk factors of stroke. The underlying mechanisms are unclear. Integrin beta3 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 beta3 in cerebrovascular remodelling and related Cl(-) signalling pathway. EXPERIMENTAL APPROACH: Cl(-) currents were recorded using a patch clamp technique. The expression of integrin beta3 in hypertensive animals was examined by Western blot and immunohistochemisty. Immunoprecipitation, cDNA and siRNA transfection were employed to investigate the integrin beta3/Src/ClC-3 signalling. KEY RESULTS: Integrin beta3 expression was up-regulated in stroke-prone spontaneously hypertensive rats, 2-kidney 2-clip hypertensive rats and angiotensin II-infused hypertensive mice. Integrin beta3 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 beta3 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 beta3, Src and ClC-3 protein. The integrin beta3/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 beta3 mediates cerebrovascular remodelling during hypertension via Src/ClC-3 signalling pathway. |
