Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, China.
FEBS J. 2010 Sep;277(18):3780-8. doi: 10.1111/j.1742-4658.2010.07779.x. Epub 2010 Aug 16.
Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger-containing transcription factor. In the present study, peripheral blood mononuclear cells and phorbol 12-myristate 13-acetate-differentiated THP-1 cells were treated with oxidized low-density lipoproteins and high-density lipoproteins to determine the expression of KLF4 and scavenger receptor class B type I (SR-BI). A full-length cDNA of KLF4 or short interference RNA against KLF4 was transfected into THP-1 cells, and the subsequent expressions of SR-BI were analysed by real-time PCR and western blot. The binding and transcriptional activities of KLF4 to the SR-BI promoter were detected by electrophoretic mobility shift assay, chromatin immunoprecipitation assay and luciferase reporter assay. The results showed that induction of KLF4 by high-density lipoproteins could promote the expression of SR-BI, resulting from the binding to putative KLF4 binding element on the promoter of SR-BI. All results indicate a potential function of KLF4 in the pathogenesis of atherosclerosis through the regulation effect on atherosclerotic-related genes.
Krüppel 样因子 4(KLF4)是一种进化上保守的含锌指转录因子。在本研究中,用氧化型低密度脂蛋白和佛波醇 12-肉豆蔻酸 13-乙酸酯诱导分化的 THP-1 细胞处理外周血单个核细胞和 THP-1 细胞,以确定 KLF4 和清道夫受体 B 类 I 型(SR-BI)的表达。将 KLF4 的全长 cDNA 或针对 KLF4 的短发夹 RNA 转染到 THP-1 细胞中,通过实时 PCR 和 Western blot 分析随后的 SR-BI 表达。通过电泳迁移率变动分析、染色质免疫沉淀分析和荧光素酶报告基因分析检测 KLF4 与 SR-BI 启动子的结合和转录活性。结果表明,高密度脂蛋白诱导的 KLF4 可促进 SR-BI 的表达,这是由于其与 SR-BI 启动子上的推定 KLF4 结合元件结合所致。所有结果均表明,KLF4 通过对动脉粥样硬化相关基因的调节作用,在动脉粥样硬化发病机制中具有潜在功能。