Kruppel-like factor （KLF） 5 mediates cyclin D1 expression and cell proliferation via interaction with c-Jun in Ang II-induced VSMCs  

作　　者：Yu LIU Jin-kun WEN Li-hua DONG Bin ZHENG Mei HAN 

机构地区：[1]Department of Biochemistry and Molecular Biology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China

出　　处：《Acta Pharmacologica Sinica》2010年第1期10-18,共9页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China （No 30670845 and 30770787）, the ＂973＂ Program of China （No 2008CB517402） and the Hebei Province Natural Science Foundation （No C2006000814 and C2005000722）.

摘　　要：Aim： To elucidate how kruppel-like factor （KLF5） activates cyclin D1 expression in Ang II-induced vascular smooth muscle cells （VSMC） proliferation. Methods： An adenoviral vector containing the full-length cDNA of KLF5 and a recombinant plasmid expressing c-Jun were constructed. MTT assay and flow cytometric analysis were used to determine the effect of Ang II on cell growth. The luciferase assay and chromatin immunoprecipitation were used to detect the relationship between KLF5 and c-Jun in transactivation of cyclin D1 gene expression. Results： Ang II upregulated the expression of KLF5 with concurrent acceleration of the cell cycle progression in VSMCs. Ang II induced KLF5 activation via the ERK and p38 MAPK pathways triggered by AT-1 receptor, High DNA binding activity and functional interaction of KLF5 and c-Jun were found in Ang II-induced VSMCs. Cotransfection of KLF5 and c-Jun expression vectors significantly increased cyclin D1 promoter activity. Conclusion： KLF5 is a downstream signal of the ERK 1/2 and p38 MAPK pathways, and activates the transcription of cyclin D1 gene via functional interaction with c-Jun in Ang II-induced VSMC proliferation.Aim： To elucidate how kruppel-like factor （KLF5） activates cyclin D1 expression in Ang II-induced vascular smooth muscle cells （VSMC） proliferation. Methods： An adenoviral vector containing the full-length cDNA of KLF5 and a recombinant plasmid expressing c-Jun were constructed. MTT assay and flow cytometric analysis were used to determine the effect of Ang II on cell growth. The luciferase assay and chromatin immunoprecipitation were used to detect the relationship between KLF5 and c-Jun in transactivation of cyclin D1 gene expression. Results： Ang II upregulated the expression of KLF5 with concurrent acceleration of the cell cycle progression in VSMCs. Ang II induced KLF5 activation via the ERK and p38 MAPK pathways triggered by AT-1 receptor, High DNA binding activity and functional interaction of KLF5 and c-Jun were found in Ang II-induced VSMCs. Cotransfection of KLF5 and c-Jun expression vectors significantly increased cyclin D1 promoter activity. Conclusion： KLF5 is a downstream signal of the ERK 1/2 and p38 MAPK pathways, and activates the transcription of cyclin D1 gene via functional interaction with c-Jun in Ang II-induced VSMC proliferation.

关 键 词：Kruppel-like factor 5 cyclin D1 angiotensin II PROLIFERATION vascular smooth muscle cells 

分 类 号：Q253[生物学—细胞生物学] Q463