Static Pressure Promotes Rat Aortic Smooth Muscle Cell Proliferation via Upregulation of Volume-Regulated Chloride Channel
Static Pressure Promotes Rat Aortic Smooth Muscle Cell Proliferation via Upregulation of Volume-Regulated Chloride Channel
复制标题
静压通过上调容量调节氯离子通道促进大鼠主动脉平滑肌细胞增殖
DOI：
10.1159/000257485
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发表时间：
2009-11
影响因子：
--
通讯作者：
庞瑞萍
中科院分区：
文献类型：
--
作者：
庞瑞萍
动脉平滑肌细胞增殖是高血压相关血管疾病发展的关键事件。虽然以前的研究发现压力本身可以促进血管平滑肌细胞的细胞增殖和DNA合成，但其机制尚不清楚。近年来越来越多的证据表明，容积调节型氯通道在众多促细胞分裂因子介导的细胞增殖调节中起着重要作用。然而，容量调节氯通道是否参与高血压诱导的血管平滑肌细胞增殖仍有待确定。在本研究中，我们发现静态压力促进大鼠主动脉平滑肌细胞增殖和细胞周期进程。静态压力处理增加容量调节的氯电流和ClC-3的表达。用药理学阻断剂抑制氯离子通道或用ClC-3反义转染敲低ClC-3可减弱压力诱发的细胞增殖和细胞周期进程。静态压力增加了主动脉平滑肌细胞活性氧（ROS）的产生。二苯基碘铵（DPI）或夹竹桃素预处理抑制压力诱导的ROS产生以及细胞增殖。此外，DPI或夹竹桃素减弱压力诱导的ClC-3蛋白和低渗激活的氯电流的上调。我们的数据表明，容量调节氯通道在静态压力诱导的细胞增殖和细胞周期进展中起着关键作用，这表明容量调节氯通道在治疗高血压伴随的血管并发症中的治疗重要性。
Arterial smooth muscle cell proliferation is a key event in the development of hypertension associated vascular disease. Although previous studies have found that pressure itself can promote cell proliferation and DNA synthesis in vascular smooth muscle cells, the mechanisms are not clear. Recent accumulating evidence indicate that volume-regulated chloride channel plays an important role in the regulation of cell proliferation induced by numerous mitogenic factors. However, whether volume-regulated chloride channel is involved in hypertension-induced vascular smooth muscle cell proliferation remains to be determined. In this study, we found that static pressure promoted rat aortic smooth muscle cell proliferation and cell cycle progression. Static pressure treatment increased volume-regulated chloride currents and ClC-3 expression. Inhibition of chloride channel with pharmacological blockers or knockdown of ClC-3 with ClC-3 antisense transfection attenuated pressure-evoked cell proliferation and cell cycle progression. Static pressure enhanced the production of reactive oxygen species (ROS) in aortic smooth muscle cells. Diphenyleneiodonium (DPI) or apocynin pretreatment inhibited pressure-induced ROS production as well as cell proliferation. Furthermore, DPI or apocynin attenuated the pressure-induced upregulation of ClC-3 protein and hypoosmolarity-activated chloride current. Our data suggest that volume-regulated chloride channel plays a critical role in static pressure-induced cell proliferation and cell cycle progression, suggesting the therapeutic importance of volume-regulated chloride channel for treatment of hypertension attendant vascular complications.
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影响因子：
5.6
作者：
Di Napoli, M;Papa, F
通讯作者：
Papa, F
影响因子：
8.5
作者：
Tang, Y. -B.;Liu, Y. -J.;Guan, Y. -Y.
通讯作者：
Guan, Y. -Y.
DOI：
10.1161/01.res.0000042062.69653.e4
发表时间：
2002-11
期刊：
Circulation Research: Journal of the American Heart Association
影响因子：
--
作者：
Guan-lei Wang;Xue-Rong Wang;Mo-Jun Lin;Hua He;Xiu-jian Lan;Y. Guan
通讯作者：
Guan-lei Wang;Xue-Rong Wang;Mo-Jun Lin;Hua He;Xiu-jian Lan;Y. Guan
影响因子：
6.1
作者：
M. Watase;M. Awolesi;J. Ricotta;B. Sumpio
通讯作者：
M. Watase;M. Awolesi;J. Ricotta;B. Sumpio
影响因子：
5.6
作者：
Klausen, Thomas Kjaer;Bergdahl, Andreas;Hoffmann, Else K.
通讯作者：
Hoffmann, Else K.