TMEM16A inhibits angiotensin Ⅱ-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner

作     者：Huaqing Zheng Xiaolong Li Xin Zeng Chengcui Huang Mingming Ma Xiaofei Lv Yajuan Zhang Lu Sun Guanlei Wang Yanhua Du Yongyuan Guan Huaqing Zheng;Xiaolong Li;Xin Zeng;Chengcui Huang;Mingming Ma;Xiaofei Lv;Yajuan Zhang;Lu Sun;Guanlei Wang;Yanhua Du;Yongyuan Guan

作者机构：Department of PharmacologyCardiac&Cerebral Vascular Research CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第12期

页      面：3994-4007页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China (grant Nos. 81872858  81773721  81573422  and 81903598) 

主　　题：TMEM16A Integrin RhoA/ROCK VSMC migration Vascular remodeling WNK1 Hypertension FAK 

摘      要：Vascular smooth muscle cell(VSMC) migration plays a critical role in the pathogenesis of many cardiovascular *** recently showed that TMEM16 A is involved in hypertensioninduced cerebrovascular ***,it is unclear whether this effect is related to the regulation of VSMC ***,we investigated whether and how TMEM16 A contributes to migration in basilar artery smooth muscle cells(BASMCs).We observed that AngⅡ increased the migration of cultured BASMCs,which was markedly inhibited by overexpression of TMEM16 ***16 A overexpression inhibited AngⅡ-induced RhoA/ROCK2 activation,and myosin light chain phosphatase(MLCP)and myosin light chain(MLC20) *** AnsⅡ-induced myosin light chain kinase(MLCK)activation was not affected by TMEM16 ***,a suppressed activation of integrinβ3/FAK pathway,determined by reduced integrinβ3 expression,FAK phosphorylation and F-actin rearrangement,was observed in TMEM16 A-overexpressing BASMCs upon AngⅡ *** to the results of TMEM16 A overexpression,silencing of TMEM16 A showed the opposite *** in vitro results were further demonstrated in vivo in basilar arteries from VSMC-specific TMEM10 A transgenic mice during AngⅡ-induced ***,we observed that the inhibitory effect of TMEM16 A on BASMC migration was mediated by decreasing the activation of WNK1,a Cl^(-)-sensitive serine/threonine *** conclusion,this study demonstrated that TMEM16 A suppressed AnsⅡ-induced BASMC migration,thus contributing to the protection against cerebrovascular remodeling during AngⅡ-infused ***16 A may exert this effect by suppressing the RhoA/ROCK2/MLCP/MLC20 and integrinβ3/FAK signaling pathways via inhibiting *** results suggest that TMEM16 A may serve as a novel therapeutic target for VSMC migration-related diseases,such as vascular remodeling.