Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hunan Clinical Research Center of Ophthalmic Disease, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
J Cell Biochem. 2020 Feb;121(2):954-962. doi: 10.1002/jcb.28978. Epub 2019 Oct 14.
Diabetic retinopathy (DR) is a serious complication of diabetes contributing to blindness in patients. Inhibiting retinal neovascularization is a potent strategy for diabetic retinopathy treatment. Reportedly, the stable expression of lin-28 homolog B (LIN28B), a member of the highly conserved RNA-binding protein LIN28 family, could promote vascular endothelial growth factor (VEGF) expression; herein, we investigated the role and mechanism of LIN28B in diabetic retinopathy progression from the perspective of microRNA (miRNA) regulation. We identified miR-152 as a miRNA that may target the LIN28B 3'-untranslated region and can be significantly downregulated under high-glucose (HG) condition. The expression of miR-152 was remarkably suppressed, whereas the expression of LIN28B was significantly increased under HG condition within both human retinal endothelial cells (hRECs) and retinal microvascular endothelial cell line (hRMECs). miR-152 overexpression significantly suppressed, while LIN28B overexpression promoted the angiogenesis and the protein levels of proangiogenesis factors in both hRECs and hRMECs. More importantly, LIN28B overexpression could remarkably attenuate the effect of miR-152 overexpression. In summary, miR-152 overexpression could inhibit HG-induced angiogenesis in both hRECs and hRMECs via targeting LIN28B and suppressing VEGF signaling. Further, in vivo experiments are needed for the application of miR-152/LIN28B axis in the treatment for diabetic retinopathy.
糖尿病性视网膜病变 (DR) 是糖尿病的严重并发症，可导致患者失明。抑制视网膜新生血管形成是治疗糖尿病性视网膜病变的有效策略。据报道，高度保守的 RNA 结合蛋白 LIN28 家族成员 lin-28 同源物 B (LIN28B) 的稳定表达可促进血管内皮生长因子 (VEGF) 的表达；在此，我们从 miRNA（miRNA）调控的角度研究了 LIN28B 在糖尿病性视网膜病变进展中的作用和机制。我们确定 miR-152 是一种可能靶向 LIN28B 3'-非翻译区的 miRNA，并且在高糖 (HG) 条件下可显著下调。在人视网膜内皮细胞 (hRECs) 和视网膜微血管内皮细胞系 (hRMECs) 中，miR-152 的表达显著受到抑制，而 LIN28B 的表达在 HG 条件下显著增加。miR-152 过表达可显著抑制，而 LIN28B 过表达可促进 hRECs 和 hRMECs 中的血管生成和促血管生成因子的蛋白水平。更重要的是，LIN28B 过表达可显著减弱 miR-152 过表达的作用。总之，miR-152 过表达可通过靶向 LIN28B 抑制 VEGF 信号通路，抑制 HG 诱导的 hRECs 和 hRMECs 中的血管生成。需要进一步的体内实验来研究 miR-152/LIN28B 轴在糖尿病性视网膜病变治疗中的应用。
