Downregulation of circRNA DMNT3B contributes to diabetic retinal vascular dysfunction through targeting miR-20b-5p and BAMBI
Downregulation of circRNA DMNT3B contributes to diabetic retinal vascular dysfunction through targeting miR-20b-5p and BAMBI
复制标题
circRNA DMNT3B 的下调通过靶向 miR-20b-5p 和 BAMBI 导致糖尿病视网膜血管功能障碍
DOI：
10.1016/j.ebiom.2019.10.004
复制
发表时间：
2019-11-01
期刊：
影响因子：
11.1
通讯作者：
Wang, Zhongfeng
中科院分区：
文献类型：
--
作者：
Zhu, Ke;Hu, Xin;Wang, Zhongfeng
背景：糖尿病视网膜病变是糖尿病的血管并发症，是视力障碍和失明的主要原因。 circRNA 作为竞争性内源性 RNA，海绵靶标 miRNA，从而影响血管疾病中的 mRNA 表达。我们研究了circDNMT3B是否以及如何参与糖尿病条件下的视网膜血管功能障碍。方法：采用qRT-PCR检测糖尿病条件下视网膜微血管内皮细胞中circDNMT3B、miR-20b-5p和BAMBI的表达。通过Western blot、Cell Counting Kit-8、Transwell、Matrigel管形成和视网膜胰蛋白酶消化实验来探讨circDNMT3B/miR-20b-5p/BAMBI在视网膜血管功能障碍中的作用。使用生物信息学分析和荧光素酶报告基因、siRNA 和过表达测定来揭示 circDNMT3B/miR-20b-5p/BAMBI 相互作用的机制。使用视网膜电图来评估视觉功能。研究结果：糖尿病条件下 miR-20b-5p 的上调促进了人视网膜微血管内皮细胞 (HRMEC) 的增殖、迁移和管形成，这是由下调的 BAMBI 介导的。在糖尿病条件下，充当 miR-20b-5p 海绵作用的 circDNMT3B 下调。 circDNMT3B 过表达可减少糖尿病大鼠的视网膜脱细胞毛细血管数量并减轻视力损伤。在糖尿病视网膜病变患者的增殖性纤维血管膜中证实了circDNMT3B和miR-20b-5p表达的变化。解读：circDNMT3B的下调通过调节miR-20b-5p和BAMBI导致糖尿病视网膜血管功能障碍，为糖尿病视网膜病变提供了潜在的治疗策略。
Background: Diabetic retinopathy, a vascular complication of diabetes mellitus, is the leading cause of visual impairment and blindness. circRNAs act as competing endogenous RNA, sponging target miRNA and thus influencing mRNA expression in vascular diseases. We investigated whether and how circDNMT3B is involved in retinal vascular dysfunction under diabetic conditions.Methods: qRT-PCR was performed to detect expression of circDNMT3B, miR-20b-5p, and BAMBI in retinal microvascular endothelial cells under diabetic conditions. Western blot, Cell Counting Kit-8, Transwell, Matrigel tube formation, and retinal trypsin digestion assays were conducted to explore the roles of circDNMT3B/miR-20b-5p/BAMBI in retinal vascular dysfunction. Bioinformatics analysis and luciferase reporter, siRNA, and overexpression assays were used to reveal the mechanisms of the circDNMT3B/miR-20b-5p/BAMBI interaction. Electroretinograms were used to evaluate visual function.Findings: Upregulation of miR-20b-5p under diabetic conditions promoted proliferation, migration, and tube formation of human retinal microvascular endothelial cells (HRMECs), which was mediated by downregulated BAMBI. Under diabetic conditions, circDNMT3B, which acts as a sponge of miR-20b-5p, is downregulated. circDNMT3B overexpression reduced retinal acellular capillary number and alleviated visual damage in diabetic rats. Changes in expression of circDNMT3B and miR-20b-5p were confirmed in the proliferative fibrovascular membranes of patients with diabetic retinopathy.Interpretation: Downregulation of circDNMT3B contributes to vascular dysfunction in diabetic retinas through regulating miR-20b-5p and BAMBI, providing a potential treatment strategy for diabetic retinopathy.