MiR-30a Inhibits the Epithelial--Mesenchymal Transition of Podocytes through Downregulation of NFATc3.
MiR-30a Inhibits the Epithelial--Mesenchymal Transition of Podocytes through Downregulation of NFATc3.
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MiR-30a 通过下调 NFATc3 抑制足细胞的上皮-间质转化。
DOI：
10.3390/ijms161024032
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发表时间：
2015-10-12
影响因子：
5.6
通讯作者：
Zhou Q
中科院分区：
文献类型：
--
作者：
Peng R;Zhou L;Zhou Y;Zhao Y;Li Q;Ni D;Hu Y;Long Y;Liu J;Lyu Z;Mao Z;Yuan Y;Huang L;Zhao H;Li G;Zhou Q
MicroRNAs(MiRNAs)在多种肾脏疾病中具有重要的调节作用，但其在足细胞损伤后上皮向间充质转化(EMT)过程中的作用尚不清楚。本研究的目的是确定miR-30a在足细胞EMT中的潜在功能，并探讨miR-30a在受损足细胞中的潜在机制。结果表明，在足细胞损伤动物模型和患者中，miR-30a的表达下调，导致间质间质标记物I型胶原、纤维连接蛋白和蜗牛的表达增强。此外，miR-30a的过度表达增加了足细胞上皮标志物(E-钙粘附素)，但降低了间充质标志物(I型胶原、纤维连接蛋白和蜗牛)。此外，我们还建立了针对非典型Wnt信号通路的重要转录因子NFATc3的miR-30a。更重要的是，我们的研究结果表明，足细胞miR-30a水平的增加抑制了NFATc3的核转位，以保护细胞骨架的紊乱或重排。综上所述，我们揭示了针对NFATc3的miR30a在调节足细胞对EMT的损伤反应中的保护作用。
MicroRNAs (miRNAs) possess an important regulating effect among numerous renal diseases, while their functions in the process of epithelial-to-mesenchymal transition (EMT) after podocyte injury remain unclear. The purpose of our study is to identify the potential functions of miR-30a in EMT of podocytes and explore the underlying mechanisms of miR-30a in the impaired podocytes. The results revealed that downregulation of miR-30a in podocyte injury animal models and patients, highly induced the mesenchymal markers of EMT including Collagen I, Fibronectin and Snail. Furthermore, overexpression of miR-30a enhances epithelial markers (E-cadherin) but diminished mesenchymal markers (Collagen I, Fibronectin and Snail) in podocytes. In addition, we established miR-30a target NFATc3, an important transcription factor of Non-canonical Wnt signaling pathway. More importantly, our findings demonstrated that the augmentation of miR-30a level in podocytes inhibits the nuclear translocation of NFATc3 to protect cytoskeleton disorder or rearrangement. In summary, we uncovered the protective function of miR30a targeting NFATc3 in the regulation of podocyte injury response to EMT.