Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450000, Henan, China.
Lab Invest. 2022 Apr;102(4):452-460. doi: 10.1038/s41374-021-00713-3. Epub 2021 Dec 16.
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.
糖尿病性白内障（DC）是糖尿病的主要眼部并发症。晶状体上皮细胞（LEC）的上皮-间充质转化（EMT）是 DC 进展的重要事件。长链非编码 RNA（lncRNA）和 microRNA 参与各种生物过程和疾病。本研究旨在探讨 lncRNA 生长停滞特异性转录物 5（GAS5）和 microRNA-204-3p（miR-204-3p）失调在高葡萄糖（HG）刺激的 LEC 致病机制中的作用。结果表明，与对照组相比，DC 患者前晶状体囊组织和 HG 处理的 LEC 中 GAS5 上调，而 miR-204-3p 下调。功能实验表明，慢病毒介导的 GAS5 耗竭以及 miR-204-3p 的过表达抑制了 HG 处理的 LEC 的迁移和 EMT。进一步的机制研究表明，lncRNA GAS5/miR-204-3p/转化生长因子-β受体 1（TGFBR1）在该过程中具有调节作用。总之，我们证明了 GAS5 的失调通过 miR-204-3p/TGFBR1 轴在 HG 条件下影响晶状体上皮细胞的迁移和 EMT。目前的研究结果可能为 DC 发展的分子机制提供新的见解。
