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Journal of Biochemistry Advance Access originally published online on July 23, 2009
Journal of Biochemistry 2009 146(5):683-691; doi:10.1093/jb/mvp115
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© The Authors 2009. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved

Angiotensin II Stimulates KLF5 Phosphorylation and its Interaction with c-Jun Leading to Suppression of p21 Expression in Vascular Smooth Muscle Cells

Ming He, Mei Han, Bin Zheng, Ya-Nan Shu and Jin-Kun Wen*

Department of Biochemistry and Molecular Biology, Hebei Medical University, No. 361, Zhongshan East Road, Shijiazhuang, 050017, China

*To whom correspondence should be addressed. Tel: +86-311-86265563, Fax: +86-311-86266180, E-mail: wjk{at}hebmu.edu.cn

Received June 30, 2009; Accepted July 6, 2009


  Abstract

Krüppel-like factor 5 (KLF5) and c-Jun are involved in angiotensin II (Ang II)-induced cell proliferation and play an important role in p21 expression. But the direct and functional implications of KLF5 and c-Jun in regulating p21 expression in vascular smooth muscle cells (VSMCs) are unclear. Here, we show that Ang II upregulated KLF5 and c-Jun expression and inhibited p21 expression in VSMCs, and silencing of KLF5 expression by KLF5-specific small interfering RNA (siRNA) neutralized the inhibitory effects of Ang II on p21 expression. Exposure of VSMCs to Ang II rapidly and strongly stimulated KLF5 phosphorylation, which results in an increase of the interaction of KLF5 with c-Jun. Treating VSMCs with PD98059, the ERK inhibitor, inhibited ERK activation and KLF5 phosphorylation as well as the interaction between KLF5 and c-Jun. Reporter analysis showed that both KLF5 and c-Jun cooperatively repressed the promoter of p21. Furthermore, KLF5 bound to its cis-elements in the p21 promoter, and meanwhile interacted with c-Jun in Ang II-induced VSMCs. These results suggest that Ang II induces KLF5 phosphorylation mediated by the ERK signalling in VSMCs, which in turn stimulates the interaction of KLF5 with c-Jun, subsequently leads to the suppression of p21 expression.

Key Words: angiotensin II, c-Jun, KLF5, p21 expession, vascular smooth muscle cells

Abbreviations: Ang II, angiotensin II; VSMC, vascular smooth muscle cell; KLF, Krüppel-like factor; KLF5, Krüppel-like factor 5; FBS, fetal bovine serum; PMSF, phenylmethylsulfonyl fluoride; SMemb, smooth muscle embryonic type myosin heavy chain-B; HDAC1, histone deacetylase 1


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