Adiponectin Upregulates Prolyl-4-Hydroxylase α1 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

来源：PLos One, 2011, 6(7): e22819.

DOI：10.1371/journal.pone.0022819

• NF-KAPPA-B
• ARTICULAR CHONDROCYTES
• TRANSCRIPTION FACTORS
• TISSUE INHIBITOR
• GENE-EXPRESSION
• IN-VIVO
• COLLAGEN
• PATHWAY
• ATHEROSCLEROSIS
• KINASE

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.

• 出版日期2011-7-29
• 单位济南市中心医院; 山东大学