Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy.
Downregulation of miR‑214-3p attenuates mesangial hypercellularity by targeting PTEN‑mediated JNK/c-Jun signaling in IgA nephropathy.
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DOI：
10.7150/ijbs.61274
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发表时间：
2021
影响因子：
9.2
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Li Y;Xia M;Peng L;Liu H;Chen G;Wang C;Yuan D;Liu Y;Liu H
肾小球系膜细胞（MC）增殖和基质扩张是伊加肾病（IgAN）的基本病理特征。然而，MC增殖的逐步机制和相关信号分子的确切集合仍不清楚。在这项研究中，我们通过miRNA测序发现了IgAN小鼠肾皮质中miR-214- 3 p的显著上调。原位杂交结果显示，miR-214- 3 p在IgAN大鼠肾皮质MC中的表达明显升高。在功能上，miR-214- 3 p的敲低减轻了IgAN小鼠的系膜细胞过多和肾脏病变。在体外，miR-214- 3 p的抑制可抑制IgAN MC增殖并阻滞G1-S细胞周期pSrogression。从机制上讲，荧光素酶报告基因测定证实了PTEN是miR-214- 3 p的直接靶标。下调miR-214- 3 p可增加PTEN表达，降低p-JNK和p-c-Jun水平，从而抑制MC增殖并改善IgAN的肾脏病变。此外，这些变化可以通过与PTEN siRNA共转染来减弱。总的来说，这些结果表明miR-214- 3 p通过直接靶向PTEN以调节JNK/c-Jun信号传导而加速IgAN中的MC增殖。因此，miR-214- 3 p可能代表IgAN的新治疗靶点。
Mesangial cell (MC) proliferation and matrix expansion are basic pathological characteristics of IgA nephropathy (IgAN). However, the stepwise mechanism of MC proliferation and the exact set of related signaling molecules remain largely unclear. In this study, we found a significant upregulation of miR-214-3p in the renal cortex of IgAN mice by miRNA sequencing. In situ hybridization analysis showed that miR-214-3p expression was obviously elevated in MCs in the renal cortex in IgAN. Functionally, knockdown of miR-214-3p alleviated mesangial hypercellularity and renal lesions in IgAN mice. In vitro, the inhibition of miR-214-3p suppressed MC proliferation and arrested G1-S cell cycle pSrogression in IgAN. Mechanistically, a luciferase reporter assay verified PTEN as a direct target of miR-214-3p. Downregulation of miR-214-3p increased PTEN expression and reduced p-JNK and p-c-Jun levels, thereby inhibiting MC proliferation and ameliorating renal lesions in IgAN. Moreover, these changes could be attenuated by co-transfection with PTEN siRNA. Collectively, these results illustrated that miR-214-3p accelerated MC proliferation in IgAN by directly targeting PTEN to modulate JNK/c-Jun signaling. Therefore, miR-214-3p may represent a novel therapeutic target for IgAN.
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影响因子：
19.6
作者：
Bao, Hao;Chen, Hao;Liu, Zhihong
通讯作者：
Liu, Zhihong
IgA肾病中miR-98-5p的上调通过细胞因子影响IgA1的糖基化
影响因子：
5.6
作者：
Liu, Di;Xia, Ming;Liu, Hong
通讯作者：
Liu, Hong
影响因子：
2.9
作者：
Liu J;Chen W;Zhang H;Liu T;Zhao L
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DOI：
10.1152/ajprenal.00287.2012
发表时间：
2013-05-01
影响因子：
4.2
作者：
Fang, Yi;Yu, Xiaofang;Ding, Xiaoqiang
通讯作者：
Ding, Xiaoqiang
影响因子：
81.5
作者：
Lai, Kar Neng;Tang, Sydney C. W.;Glassock, Richard J.
通讯作者：
Glassock, Richard J.