Up-regulation of VLDL Receptor Expression and Its Signaling Pathway Induced by VLDL and β-VLDL  

作　　者：刘志国 李和 李映红 王燕 宗义强 冯友梅 冯宗忱 邓耀祖 屈伸 

机构地区：[1]Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology [2]Department of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2009年第1期1-7,共7页华中科技大学学报（医学英德文版）

基　　金：supported by grant from National Natural Sciences Foundation of China (No. 39970307);Hubei Provincial Natural Sciences Foundation of China (No. 2005ABA092).

摘　　要：Very low density lipoprotein receptor （VLDLR） is thought to participate in the pathogenesis of atherosclerosis induced by VLDL and β-VLDL. The present study was undertaken to elucidate the effects of VLDL and β-VLDL on VLDLR expression and its signaling pathway. RAW264.7 cells were incubated with VLDL and β-VLDL. The expression of VLDLR mRNA was detected by RT-PCR. The transcriptional activity of VLDLR gene was detected in recombinant plasmid pGL4.2VR-luciferase transfected RAW264.7. Western blot assay was used to detect the changes of phosphorylated ERK1/2 protein. Inhibitors or activators were used to observe the signal pathway involving VLDLR expression regulation. The results showed that VLDL and β-VLDL stimulated ERK1/2 activity in a PKC-dependent manner. VLDL or β-VLDL-induced VLDLR expression on macrophages was extremely abolished by inhibitors ERK1/2 or PKC. Our findings revealed that VLDL or β-VLDL-induced VLDLR expression via PKC/ERK cascades and the effect was linked to the transcriptional activation of VLDLR gene promoter.Very low density lipoprotein receptor （VLDLR） is thought to participate in the pathogenesis of atherosclerosis induced by VLDL and β-VLDL. The present study was undertaken to elucidate the effects of VLDL and β-VLDL on VLDLR expression and its signaling pathway. RAW264.7 cells were incubated with VLDL and β-VLDL. The expression of VLDLR mRNA was detected by RT-PCR. The transcriptional activity of VLDLR gene was detected in recombinant plasmid pGL4.2VR-luciferase transfected RAW264.7. Western blot assay was used to detect the changes of phosphorylated ERK1/2 protein. Inhibitors or activators were used to observe the signal pathway involving VLDLR expression regulation. The results showed that VLDL and β-VLDL stimulated ERK1/2 activity in a PKC-dependent manner. VLDL or β-VLDL-induced VLDLR expression on macrophages was extremely abolished by inhibitors ERK1/2 or PKC. Our findings revealed that VLDL or β-VLDL-induced VLDLR expression via PKC/ERK cascades and the effect was linked to the transcriptional activation of VLDLR gene promoter.

关 键 词：VLDLR signal transduction transcriptional regulation 

分 类 号：R341[医药卫生—基础医学] R543