期刊
LABORATORY INVESTIGATION
卷 102, 期 4, 页码 452-460出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/s41374-021-00713-3
关键词
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资金
- National Natural Science Foundation of China [81970786, 81670836]
- Medical Science and Technology Project Jointly Built of Henan Province [LHGJ20190196]
- Key Scientific Research Projects of Henan Colleges and Universities [20A320031]
DC is a major ocular complication of diabetes, characterized by EMT of LECs. GAS5 and miR-204-3p are involved in the pathogenic mechanism through regulating migration and EMT of LECs induced by HG. The dysregulation of GAS5 impacts lens epithelial cell migration and EMT under HG conditions via the miR-204-3p/TGFBR1 axis.
Diabetic cataract (DC) is a major ocular complication secondary to diabetes mellitus. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is an important event in DC progression. Long non-coding RNAs (lncRNAs) and microRNAs are involved in various biological processes and disorders. The aim of this study was to investigate the roles of lncRNA growth arrest-specific transcript 5 (GAS5) and microRNA-204-3p (miR-204-3p) deregulation in the pathogenic mechanism of high glucose (HG)-stimulated LECs. The results show that GAS5 was up-regulated, whereas miR-204-3p was down-regulated in anterior lens capsule tissues of DC patients and in HG-treated LECs compared to their controls, respectively. Functional experiments suggest that the lentivirus-mediated depletion of GAS5, as well as overexpression of miR-204-3p, suppressed migration and EMT in HG-treated LECs. Further mechanistic studies revealed that lncRNA GAS5/miR-204-3p/type 1 receptor of transforming growth factor-beta (TGFBR1) has a regulatory role in the process. Collectively, we demonstrated that dysregulation of GAS5 affects lens epithelial cell migration and EMT under HG conditions via the miR-204-3p/TGFBR1 axis. The current findings may provide new insights into the molecular mechanisms of DC development. Under high-glucose conditions, LECs obtain characteristics of mesenchymal cells such as high migratory capacity and invasiveness, which is the foundational basis for DC progression. The authors demonstrated that lncRNA GAS5 facilitates high glucose-induced lens epithelial cell migration and epithelial-to-mesenchymal transition by regulating the miR-204-3p/TGFBR1 axis. This study, therefore, provides novel insights into the pathogenesis of DCs.
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