Adiponectin upregulates prolyl-4-hydroxylase α1 expression in interleukin 6-stimulated human aortic smooth muscle cells by regulating ERK 1/2 and Sp1.
Adiponectin upregulates prolyl-4-hydroxylase α1 expression in interleukin 6-stimulated human aortic smooth muscle cells by regulating ERK 1/2 and Sp1.
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DOI：
10.1371/journal.pone.0022819
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Li L;Zhang K;Cai XJ;Feng M;Zhang Y;Zhang M
脂联素是一种抗动脉粥样硬化的脂肪因子，其抑制斑块形成的机制尚不完全清楚。细胞外基质（ECM）可能在动脉粥样硬化的发病机制中发挥作用。本研究探讨脂联素对白细胞介素6（IL-6）刺激的人主动脉平滑肌细胞（HASMCs）脯氨酰-4-羟化酶（P4 H）合成的影响及其机制。RT-PCR检测P4 H α1 mRNA水平，Western blot检测磷酸化细胞外信号调节激酶1/2（ERK 1/2）和P4 H α1蛋白水平，电泳迁移率变动分析检测特异性蛋白1（Sp1）的活化，免疫荧光分析检测Sp1的亚细胞定位。脂联素可显著增加IL-6刺激的HASMCs中P4 H α1 mRNA和蛋白水平，且呈剂量和时间依赖性。ERK 1/2和Sp1在脂联素上调IL-6刺激的HASMCs P4 H α1表达中起重要作用。脂联素可消除IL-6对Ⅲ型胶原的影响，提示P4 H α1可能是前胶原多肽链折叠成稳定胶原的关键。脂联素通过Sp1-ERK 1/2-P4 H α1依赖性途径减弱IL-6抑制的HASMCs P4 H α1合成并稳定胶原形成
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). P4Hα1 mRNA level was quantified by RT-PCR, the protein levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and P4Hα1 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 P4Hα1 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 P4Hα1 expression in IL-6-stimulated HASMCs. Adiponectin abrogated the effects of IL-6 on collagen III level, which may indicate that P4Hα1 is essential for folding the procollagen polypeptide chains into stabilized collagen. Adiponectin attenuates IL-6–inhibited P4Hα1 synthesis and stabilizes collagen formation in HASMCs through a Sp1-ERK1/2-P4Hα1-dependent pathway.
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影响因子：
4.9
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