Krüppel 样因子 5（KLF）5 通过与 Ang II 诱导的 VSMCs 中的 c-Jun 相互作用来介导细胞周期蛋白 D1 的表达和细胞增殖。
Krüppel-like factor (KLF) 5 mediates cyclin D1 expression and cell proliferation via interaction with c-Jun in Ang II-induced VSMCs.
机构信息
Department of Biochemistry and Molecular Biology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
出版信息
Acta Pharmacol Sin. 2010 Jan;31(1):10-8. doi: 10.1038/aps.2009.185. Epub 2009 Dec 28.
Abstract
AIM
To elucidate how krüppel-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.
摘要
目的
阐明 Krüppel 样因子（KLF5）如何激活血管平滑肌细胞（VSMC）增殖中血管紧张素Ⅱ（Ang II）诱导的细胞周期蛋白 D1 的表达。
方法
构建了一个含有全长 KLF5 cDNA 的腺病毒载体和一个表达 c-Jun 的重组质粒。MTT 检测和流式细胞术分析用于确定 Ang II 对细胞生长的影响。荧光素酶检测和染色质免疫沉淀用于检测 KLF5 和 c-Jun 在 cyclin D1 基因表达的反式激活之间的关系。
结果
Ang II 上调了 KLF5 的表达，同时加速了 VSMC 中的细胞周期进程。Ang II 通过 AT-1 受体触发的 ERK 和 p38 MAPK 途径激活 KLF5。在 Ang II 诱导的 VSMC 中发现了 KLF5 和 c-Jun 的高 DNA 结合活性和功能相互作用。共转染 KLF5 和 c-Jun 表达载体显著增加了 cyclin D1 启动子活性。
结论
KLF5 是 ERK 1/2 和 p38 MAPK 通路的下游信号，通过与 Ang II 诱导的 VSMC 增殖中 c-Jun 的功能相互作用，激活 cyclin D1 基因的转录。
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2
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3
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