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(Circulation Research. 2002;91:e28.)
© 2002 American Heart Association, Inc.

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Deficiency in ClC-3 Chloride Channels Prevents Rat Aortic Smooth Muscle Cell Proliferation

Guan-Lei Wang, Xue-Rong Wang, Mo-Jun Lin, Hua He, Xiu-Jian Lan, Yong-Yuan Guan

From the Department of Pharmacology, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, People’s Republic of China.

Correspondence to Dr Yong-Yuan Guan, Prof, Dept of Pharmacology, Sun Yat-Sen University, Zhongshan Medical College, 74 Zhongshan 2 Rd, Guangzhou, Guangdong 510089, P.R. China. E-mail yyguan{at}gzsums.edu.cn

Recent growing evidence suggests that chloride (Cl^-) channels are critical to the cell cycle. In cultured rat aortic vascular smooth muscle cells (VSMCs), we have previously found that Cl^- channel blockers inhibit endothelin-1 (ET-1)–induced cell proliferation. The present study was designed to further identify the specific Cl^- channels responsible for VSMC proliferation. Due to the lack of a specific blocker or opener of any known Cl^- channels, we used the antisense strategy to investigate the potential role of ClC-3, a member of the voltage-gated Cl^- channel gene family, in cell proliferation of cultured rat aortic VSMCs. With [³H]-thymidine incorporation and immunoblots, we found that ET-1–induced cell proliferation was parallel to a significant increase in the endogenous expression of ClC-3 protein. Transient transfection of rat aortic VSMCs with antisense oligonucleotide specific to ClC-3 caused an inhibition in ET-1–induced expression of ClC-3 protein and cell proliferation of VSMCs in the same concentration- and time-dependent pattern, whereas sense and missense oligonucleotides resulted in no effects on ClC-3 protein expression and cell proliferation. These results strongly suggest that ClC-3 may be the Cl^- channel involved in VSMC proliferation and thus provide compelling molecular evidence linking a specific Cl^- channel to cell proliferation. The full text of this article is available at http://www.circresaha.org.

Key Words: vascular smooth muscle • chloride channel • proliferation • gene expression

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