标题：Adiponectin Upregulates Prolyl-4-Hydroxylase alpha 1 Expression in Interleukin 6-Stimulated Human Aortic Smooth Muscle Cells by Regulating ERK 1/2 and Sp1
作者：Li, Li; Zhang, Ke; Cai, Xiao-Jun; Feng, Min; Zhang, Yun; Zhang, Mei
作者机构：[Li, Li; Zhang, Ke; Cai, Xiao-Jun; Feng, Min; Zhang, Yun; Zhang, Mei] Shandong Univ, Qilu Hosp, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Min 更多
通讯作者地址：[Li, L]Shandong Univ, Qilu Hosp, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Jinan 250100, Shandong, Peoples R China.
摘要：Adiponectin is an anti-atherogenic adipokine that inhibits the development of plaque by mechanisms that are not completely understood. Extracellular matrix (ECM) may have a role in the pathogenesis of atherosclerosis. We explored the effect and mechanisms of adiponectin on the synthesis of prolyl-4-hydroxylase (P4H) in interleukin 6 (IL-6)-stimulated human aortic smooth muscle cells (HASMCs). P4H alpha 1 mRNA level was quantified by RT-PCR, the protein levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and P4H alpha 1 were quantified by western blot analysis, and activation of specific protein 1 (Sp1) was determined by electrophoretic mobility shift assay and subcellular localization of Sp1 by immunofluorescence analysis. Adiponectin significantly increased P4H alpha 1 mRNA and protein levels in IL-6-stimulated HASMCs in a dose-and time-dependent manner. As well, ERK1/2 and Sp1 played a crucial role in the effect of adiponectin upregulating P4H alpha 1 expression in IL-6-stimulated HASMCs. Adiponectin abrogated the effects of IL-6 on collagen III level, which may indicate that P4H alpha 1 is essential for folding the procollagen polypeptide chains into stabilized collagen. Adiponectin attenuates IL-6-inhibited P4H alpha 1 synthesis and stabilizes collagen formation in HASMCs through a Sp1-ERK1/2P4H alpha 1-dependent pathway.