MicroRNA-30a Regulation of Epithelial-Mesenchymal Transition in Diabetic Cataracts Through Targeting SNAI1.
MicroRNA-30a Regulation of Epithelial-Mesenchymal Transition in Diabetic Cataracts Through Targeting SNAI1.
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MicroRNA-30a 通过靶向 SNAI1 调节糖尿病白内障的上皮间质转化
DOI：
10.1038/s41598-017-01320-3
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发表时间：
2017-04-25
影响因子：
4.6
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Zhang L;Wang Y;Li W;Tsonis PA;Li Z;Xie L;Huang Y
上皮间质转化（EMT）是一个高度保守的和基本的过程中的发展，纤维化和转移。在此过程中，上皮细胞失去其形态和转录程序，并转分化为间充质细胞。有报道称，白内障形成过程中透镜上皮细胞发生EMT，microRNA对基因的调控与透镜发育相关。然而，糖尿病性白内障中这种调节的分子机制仍需研究。在本研究中，E-cadherin在糖尿病性白内障组织和体外模型中表达下调，而α-SMA和vimentin表达上调，提示EMT参与了糖尿病性白内障的形成。miR-30 a在糖尿病性白内障组织中表达显著下调。在我们的体外糖尿病白内障模型中，miR-30 a-5 p的过表达降低了SNAI 1（一种已知的EMT调节剂）以及波形蛋白和α-SMA的表达。结论：EMT参与了糖尿病性白内障的发生，上调miR-30 a可通过靶向透镜上皮细胞SNAI 1抑制EMT，使miR-30 a成为糖尿病性白内障治疗的新靶点。
Epithelial-mesenchymal transition (EMT) is a highly conserved and fundamental process in development, fibrosis, and metastasis. During the process, epithelial cells lose their morphology and transcriptional program, and transdifferentiate to mesenchymal cells. It has been reported that lens epithelial cells undergo EMT during cataract formation, and regulation of microRNAs on genes is associated with lens development. However, the molecular mechanisms of this regulation in diabetic cataract still need to be investigated. In the present study, the expression of E-cadherin was downregulated, while the expression of alpha-SMA and vimentin was upregulated in diabetic cataract tissues and thein vitromodel, suggesting the involvement of EMT in diabetic cataract formation. Results of miRNA profiling demonstrated that miR-30a was markedly downregulated in diabetic cataract tissues. Overexpression of miR-30a-5p decreased SNAI1, a known modulator of EMT, and the expression of vimentin and alpha-SMA in our diabetic cataract modelin vitro. It is concluded that EMT is involved in human diabetic cataract, and upregulation of miR-30a can repress EMT through its targeting of SNAI1 in lens epithelial cells, which make miR-30a a novel target of therapeutic intervention for human diabetic cataract.