MiR542-3p Regulates the Epithelial-Mesenchymal Transition by Directly Targeting BMP7 in NRK52e.

MiR542-3p Regulates the Epithelial-Mesenchymal Transition by Directly Targeting BMP7 in NRK52e.
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MiR542-3p 通过直接靶向 NRK52e 中的 BMP7 调节上皮-间质转化

DOI:
10.3390/ijms161126075
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发表时间:
2015-11-24
影响因子:
5.6
通讯作者:
Zhou Q
Zhou Q
中科院分区:
生物学2区
文献类型:
--
作者:
Liu Z;Zhou Y;Yuan Y;Nie F;Peng R;Li Q;Lyu Z;Mao Z;Huang L;Zhou L;Li Y;Hao J;Ni D;Jin Q;Long Y;Ju P;Yu W;Liu J;Hu Y;Zhou Q

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越来越多的证据表明,miRNAs与肾纤维化和上皮-间质转化(EMT)密切相关,但miRNAs在肾纤维化中的作用机制尚不清楚。在本研究中,我们发现miR542 - 3p可以通过靶向骨形态发生蛋白7(BMP7)的3 ′ UTR下调BMP7的表达,从而促进EMT的发生。首先,实时荧光定量PCR结果显示,miR542 - 3p在体外和体内肾纤维化中显著上调。Western blot结果显示miR542 - 3p可促进NRK52e细胞的EMT。此外,我们通过Dual-Luciferase报告基因分析证实了在抗肾纤维化和抑制EMT进展中起关键作用的BMP 7是miR542 - 3p的靶点,Western印迹分析也是如此。miR542 - 3p调节EMT的作用也可以通过在NRK52e细胞中瞬时过表达BMP 7来抑制。综上所述,miR542 - 3p可能是通过直接靶向BMP 7诱导EMT的关键介质。
Accumulating evidence demonstrated that miRNAs are highly involved in kidney fibrosis and Epithelial-Eesenchymal Transition (EMT), however, the mechanisms of miRNAs in kidney fibrosis are poorly understood. In this work, we identified that miR542-3p could promote EMT through down-regulating bone morphogenetic protein 7 (BMP7) expression by targeting BMP7 3′UTR. Firstly, real-time PCR results showed that miR542-3p was significantly up-regulated in kidney fibrosis in vitro and in vivo. Moreover, Western blot results demonstrated that miR542-3p may promote EMT in the NRK52e cell line. In addition, we confirmed that BMP7, which played a crucial role in anti-kidney fibrosis and suppressed the progression of EMT, was a target of miR542-3p through Dual-Luciferase reporter assay, as did Western blot analysis. The effects of miR542-3p on regulating EMT could also be suppressed by transiently overexpressing BMP7 in NRK52e cells. Taken together, miR542-3p may be a critical mediator of the induction of EMT via directly targeting BMP7.