Abstract
Purpose:
One of the most common complications of diabetes mellitus (DM) is cataracts and diabetic patients also tend to develop cataracts earlier in life than those without DM. Also it is not clear how epithelial-to-mesenchymal transition (EMT) contributes to diabetic cataract. This study investigated the role of microRNA (miRNA) in regulating EMT during human diabetic cataract.
Methods:
A miRCURY LNA microRNA array was used to evaluate the miRNA profiles of human diabetic cataract tissues and normal attached lens epithelial cells (LECs). An in vitro human donor capsular bag model was used to investigate the role of miRNAs in the EMT during diabetic cataract. The expression of Snail1/2 and a panel of EMT markers were detected by Western blot and quantitative RT-PCR.
Results:
Down-regulation of E-cadherin and up-regulation of vimentin and alpha smooth muscle actin (α-SMA) were found in diabetic cataract tissues and normal LECs treated with high glucose, suggesting EMT may be involved in diabetic cataract. The results of miRNA profiling in human diabetic cataract tissues and normal attached LECs demonstrated that, among other miRNAs, miR-30a expression was down-regulated. Using bioinformatics, we identified Snail1/2, the key mediators of TGF-beta signaling, as the predicted target of miR-30a. Overexpression of miR-30a in primary LECs increased Ecadherin expression and decreased the expression of vimentin and α-SMA. Furthermore, miR-30a overexpression enhanced the repression of TGF-beta 2-induced EMT in the presence of Snail1/2 small interfering RNA.
Conclusions:
In this study, we reported EMT is involved in human diabetic cataract. Also, these results provide firm evidence of a role for miR-30a in the direct regulation of EMT through its targeting of Snail1/2 and miR-30a may be a novel target for human diabetic cataract therapeutic intervention.