PubMed 19910686

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC3 , ClvC4

Title: Static pressure promotes rat aortic smooth muscle cell proliferation via upregulation of volume-regulated chloride channel.

Authors: Jie-Sheng Qian, Rui-Ping Pang, Kang-Shun Zhu, Da-Yue Liu, Zhen-Ran Li, Chun-yu Deng, Shen-Ming Wang

Journal, date & volume: Cell. Physiol. Biochem., 2009 , 24, 461-70

PubMed link:

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.