Yu Xin, Li Zheng, Chen Guang, Wu William Ka Kei
Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Curr Vasc Pharmacol. 2015;13(5):679-86. doi: 10.2174/1570161113666150123112751.
Abnormal proliferation of vascular smooth muscle cells (VSMCs) contributes significantly to the pathogenesis of atherosclerosis. MiR-10b has recently emerged as a critical mediator in regulating cell proliferation in many diseases. In our study, miR-10b expression was up-regulated in VSMCs isolated from atherosclerotic plaques, as well as in PDGFstimulated VSMCs.Overexpression of miR-10b promoted cell proliferation of VSMCs. Furthermore, we identified the Tat-interacting protein 30 (TIP30) as a direct target gene of miR-10b. TIP30 was down-regulated in VSMCs isolated from atherosclerosis plaques, as well as in proliferative VSMCs. Knockdown of TIP30 promoted VSMCs proliferation. In addition, miR-10b induced TIP30 down-regulation was accompanied by increased Akt phosphorylation. Akt was critical for miR-10b-mediated VSMCs proliferation. Our results demonstrated that miR-10b contributed to abnormal VSMCs proliferation through inhibiting the Akt pathway by targeting TIP30 in atherosclerosis. The modulation of miR-10b in VSMCs provides a potential target for the therapy of atherosclerosis.
血管平滑肌细胞(VSMCs)的异常增殖在动脉粥样硬化的发病机制中起重要作用。miR-10b最近已成为许多疾病中调节细胞增殖的关键介质。在我们的研究中,从动脉粥样硬化斑块分离的VSMCs以及血小板衍生生长因子(PDGF)刺激的VSMCs中,miR-10b表达上调。miR-10b的过表达促进了VSMCs的细胞增殖。此外,我们确定Tat相互作用蛋白30(TIP30)是miR-10b的直接靶基因。从动脉粥样硬化斑块分离的VSMCs以及增殖性VSMCs中,TIP30表达下调。敲低TIP30促进了VSMCs增殖。此外,miR-10b诱导的TIP30下调伴随着Akt磷酸化增加。Akt对miR-10b介导的VSMCs增殖至关重要。我们的结果表明,在动脉粥样硬化中,miR-10b通过靶向TIP30抑制Akt途径,从而导致VSMCs异常增殖。调节VSMCs中的miR-10b为动脉粥样硬化的治疗提供了一个潜在靶点。