Sun Huiyan, Cai Songzhi, Zhang Mei, Zhao Juan, Wei Shuping, Luo Yuyu, Meng Xiangyan, Zhou Xin, Li Yuming, Zhang Wencheng
Department of Physiology and Pathophysiology, Logistics University of Chinese People's Armed Police Force, Huizhihuan Road 1, Dongli District, Tianjin, 300309, China.
Department of Cardiology, Affiliated Hospital, Logistics University of Chinese People's Armed Police Force, Chenglin Road 220, Dongli District, Tianjin, 300162, China.
Cell Biol Int. 2017 Jul;41(7):739-748. doi: 10.1002/cbin.10768.
MiR-206 has been found to play a critical role in skeletal muscle proliferation, differentiation, and regeneration. However, little is known about the function of miR-206 in vascular smooth muscle cells (VSMCs) biology. In this study, we will investigate its roles in phenotypic switching of VSMCs and neointimal lesion formation. First, we identified the expression of miR-206 in VSMCs treated with various concentrations of TGFβ1 and in rat carotid arteries after angioplasty by using qPCR. TGFβ1 inhibited the expression of miR-206 and TGFβ1 inhibitor induced miR-206 expression. In VSMCs of injured vascular walls, miR-206 expression was upregulated. Then, we overexpressed miR-206 using lentivirus Lv-rno-mir-206 and knocked down miR-206 using LV-rno-mir-206-inhibitor in rat carotid arteries after angioplasty. Overexpression of miR-206 resulted in decreasing SM22α expression in VSMCs in vitro and knockdown of miR-206 suppressed neointimal lesion formation in vivo. Finally, ZFP580 (zinc finger protein 580) was identified as the direct target of miR-206 in VSMCs by using luciferase report assay. The results indicate that miR-206 is involved in phenotypic switching of VSMCs and neointimal lesion formation after angioplasty through targeting ZFP580. These findings may provide a novel therapeutic target in post-angioplasty restenosis.
已发现miR-206在骨骼肌增殖、分化和再生中起关键作用。然而，关于miR-206在血管平滑肌细胞（VSMC）生物学中的功能知之甚少。在本研究中，我们将研究其在VSMC表型转换和新生内膜病变形成中的作用。首先，我们通过qPCR鉴定了用不同浓度TGFβ1处理的VSMC以及血管成形术后大鼠颈动脉中miR-206的表达。TGFβ1抑制miR-206的表达，而TGFβ1抑制剂诱导miR-206表达。在受损血管壁的VSMC中，miR-206表达上调。然后，我们在血管成形术后的大鼠颈动脉中使用慢病毒Lv-rno-mir-206过表达miR-206，并使用LV-rno-mir-206抑制剂敲低miR-206。miR-206的过表达导致体外VSMC中SM22α表达降低，而miR-206的敲低抑制体内新生内膜病变形成。最后，通过荧光素酶报告基因检测确定ZFP580（锌指蛋白580）为VSMC中miR-206的直接靶标。结果表明，miR-206通过靶向ZFP580参与血管成形术后VSMC的表型转换和新生内膜病变形成。这些发现可能为血管成形术后再狭窄提供新的治疗靶点。
