MicroRNA-206 regulates vascular smooth muscle cell phenotypic switch and vascular neointimal formation
MicroRNA-206 regulates vascular smooth muscle cell phenotypic switch and vascular neointimal formation
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MicroRNA-206调节血管平滑肌细胞表型转换和血管新生内膜形成
DOI：
10.1002/cbin.10768
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发表时间：
2017-07-01
影响因子：
3.9
通讯作者：
Zhang, Wencheng
中科院分区：
文献类型：
--
作者：
Sun, Huiyan;Cai, Songzhi;Zhang, Wencheng
已经发现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，我们将探讨其在血管平滑肌细胞表型转换和新生内膜病变形成中的作用。首先，我们通过使用qPCR鉴定了用不同浓度的TGF β 1处理的VSMC和血管成形术后大鼠颈动脉中miR-206的表达。TGF β 1抑制miR-206的表达，TGF β 1抑制剂诱导miR-206的表达。在受损血管壁的VSMC中，miR-206表达上调。然后，我们使用慢病毒Lv-rno-mir-206在血管成形术后的大鼠颈动脉中过表达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SM 22 α表达降低，而miR-206的敲低抑制体内新生内膜损伤形成。最后，通过荧光素酶报告试验，证实ZFP 580（zinc finger protein 580）是miR-206在VSMCs中的直接靶点。结果表明，miR-206通过靶向ZFP 580参与血管成形术后VSMC的表型转换和新生内膜损伤的形成。这些发现可能为血管成形术后再狭窄的治疗提供新的靶点。
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 TGF beta 1 and in rat carotid arteries after angioplasty by using qPCR. TGF beta 1 inhibited the expression of miR-206 and TGF beta 1 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 SM22 alpha 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.