Adiponectin attenuates the osteoblastic differentiation of vascular smooth muscle cells through the AMPK/mTOR pathway
Adiponectin attenuates the osteoblastic differentiation of vascular smooth muscle cells through the AMPK/mTOR pathway
复制标题
脂联素通过 AMPK/mTOR 通路减弱血管平滑肌细胞的成骨分化
DOI：
10.1016/j.yexcr.2014.02.016
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发表时间：
2014-05-01
影响因子：
3.7
通讯作者：
Liu, You-Shuo
中科院分区：
文献类型：
--
作者：
Zhan, Jun-Kun;Wang, Yan-Jiao;Liu, You-Shuo
血管钙化在外周动脉疾病和冠状动脉疾病患者中很常见。血管平滑肌细胞（VSMCs）的成骨分化在血管钙化中起重要作用。脂联素通过调节mTOR活性对VSMCs的成骨分化具有保护作用。然而，脂联素调节mTOR信号的上游和下游信号分子尚未在成骨分化的VSMCs中确定。本研究采用β-甘油磷酸（beta-glycerophosphate，beta-GP）诱导建立VSMC分化模型。茜素红S染色鉴定矿化。蛋白质表达和磷酸化通过Western blot或免疫荧光检测。脂联素减弱β-GP处理的VSMCs的成骨分化和矿化。脂联素通过增加p-AMPK α水平抑制VSMCs向成骨细胞分化。AMPK抑制剂预处理可阻断脂联素对VSMCs向成骨细胞分化的作用，而AMPK激活剂预处理可增强脂联素对VSMCs向成骨细胞分化的作用。脂联素上调TSC 2表达，下调mTOR和S6 K1磷酸化。脂联素通过调节AMPK、TSC 2、mTOR、S6 K1信号通路，显著抑制VSMCs的成骨分化和钙化。(c)2014爱思唯尔公司All rights reserved.
Vascular calcification is common in patients with peripheral artery diseases and coronary artery diseases. The osteoblastic differentiation of vascular smooth muscle cells (VSMCs) contributes significantly to vascular calcification. Adiponectin has been demonstrated to exert a protective effect in osteoblastic differentiation of VSMCs through regulating mTOR activity. However, the upstream and downstream signaling molecules of adiponectin-regulated mTOR signaling have not been identified in VSMCs with osteoblastic differentiation. In this study, the VSMC differentiation model was established by beta-glycerophosphate (beta-GP) induction. The mineralization was identified by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot or immunofluorescence. Adiponectin attenuated osteoblastic differentiation and mineralization of beta-GP-treated VSMCs. Adiponectin inhibited osteoblastic differentiation of VSMCs through increasing the level of p-AMPK alpha. Pretreatment of VSMCs with AMPK inhibitor blocked while AMPK activator enhanced the effect of adiponectin on osteoblastic differentiation of VSMCs. Adiponectin upregulated TSC2 expression and downregulated mTOR and S6K1 phosphorylation in p-GP-treated VSMCs. Adiponectin treatment significantly attenuates the osteoblastic differentiation and calcification of VSMCs through modulation of AMPK TSC2 mTOR S6K1 signal pathway. (c) 2014 Elsevier Inc. All rights reserved.