Involvement of chloride channels in IGF-I-induced proliferation of porcine arterial smooth muscle cells

Gang Cheng, Min Jung Kim, Guanghong Jia, Devendra K. Agrawal

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Objective: The existence of Cl- channels in vascular smooth muscle cells (VSMCs) has been increasingly investigated, but the biological functions are not yet clear. Insulin-like growth factor (IGF)-I affects proliferation and migration of VSMCs, and dysregulation of this axis may be involved in atherogenesis and intimal hyperplasia. We examined the effects of Cl- channel blockers on IGF-I-induced proliferation in porcine VSMCs. The siRNA approach was used to support the role of ClC-2, a member of the volume-regulated Cl- channel family, in cell proliferation of VSMCs. Methods and results: The IGF-I-induced VSMC proliferation was significantly suppressed by the Cl- channel blockers NPPB and IAA94 but not by DIDS. IGF-I-induced cell proliferation parallels a significant increase in the endogenous expression of ClC-2 mRNA and protein. Inhibitors of PI3-kinase, LY294002 and wortmannin, significantly attenuated the IGF-I-upregulated ClC-2 expression and cell proliferation. We observed ClC-2-like Cl- current, and this current was augmented by IGF-I. SiRNA specifically targeted to ClC-2 abolished IGF-I-induced cell proliferation. Conclusion: Our data demonstrate that ClC-2 plays a role in IGF-1-induced regulation of VSMC proliferation in cardiovascular diseases.

Original languageEnglish
Pages (from-to)198-207
Number of pages10
JournalCardiovascular Research
Volume73
Issue number1
DOIs
StatePublished - Jan 1 2007

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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