MicroRNA-29b regulates TGF-β1-mediated epithelial-mesenchymal transition of retinal pigment epithelial cells by targeting AKT2
MicroRNA-29b regulates TGF-β1-mediated epithelial-mesenchymal transition of retinal pigment epithelial cells by targeting AKT2
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MicroRNA-29b 通过靶向 AKT2 调节 TGF-β1 介导的视网膜色素上皮细胞上皮间质转化。
DOI：
10.1016/j.yexcr.2014.09.026
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发表时间：
2016-07-15
影响因子：
3.7
通讯作者：
Wang, Fang
中科院分区：
文献类型：
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作者：
Li, Min;Li, Hui;Wang, Fang
microRNA（miRNA）在增生性玻璃体视网膜病变（PVR）进展中的作用尚未得到广泛研究，尤其是在视网膜色素上皮间质转化（EMT）中，EMT是PVR形成的主要原因。在本研究中，我们首先研究了转化生长因子β 1（TGF-β 1）介导的ARPE-19细胞EMT中的miRNA表达谱。在5种变化的miRNAs中，miR-29 b表现出最显著的下调。miR-29 b的表达增强可通过靶向Akt 2逆转TGF-β 1诱导的EMT。Akt 2下调可抑制TGF-β 1诱导的EMT。抑制miR-29 b可直接诱导ARPE-19细胞发生EMT，表现为细胞表型转变、α-平滑肌肌动蛋白（alpha-smooth muscle actin，alpha-SMA）表达上调、E-cadherin和E-occludin-1（ZO-1）表达下调，细胞迁移能力增强。Akt 2-shRNA还抑制了miR-29抑制剂诱导的EMT过程。这些数据表明，miR-29 b通过靶向Akt 2在ARPE-19细胞中TGF-β 1介导的EMT中起重要作用。(C)2016由Elsevier Inc.出版
The role of microRNA (miRNA) in proliferative vitreoretinopathy (PVR) progression has not been studied extensively, especially in retinal pigment epithelial mesenchymal transition (EMT) which is the main reason for formation of PVR. In this study, we first investigated the miRNA expression profile in transforming growth factor beta I (TGF-beta 1) mediated EMT of ARPE-19 cells. Among the five changed miRNAs, miR-29b showed the most significant downregulation. Enhanced expression of miR-29b could reverse TGF-beta 1 induced EMT through targeting Akt2. Akt2 downregulation could inhibit TGF-beta 1-induced EMT. Furthermore, inhibition of miR-29b in ARPE-19 cells directly triggered EMT process, which characterized by the phenotypic transition and the upregulation of alpha-smooth muscle actin (alpha-SMA) and down regulation of E-cadherin and zona occludin-1 (ZO-1) with increased cell migration. Akt2-shRNA also inhibited miR-29 inhibitor-induced EMT process. These data indicate that miR-29b plays an important role in TGF-beta 1-mediated EMT in ARPE-19 cells by targeting Akt2. (C) 2016 Published by Elsevier Inc.