Journal Article

Circular RNA-ZNF532 regulates diabetes-induced retinal pericyte degeneration and vascular dysfunction

Zhao, Chen, Xu, Shan-Shan, Jiang, Qin, Yan, Biao, Liu, Bai-Hui, Sun, Ya-Nan, Yao, Mu-Di, Li, Xiu-Miao, Zhang, Shu-Jie, Shan, Kun, Ge, Hui-Min, Li, Chao-Peng, Yao, Jin, Liu, Chang

2020

Overview

Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Vascular pericyte degeneration is the predominant clinical manifestation of DR, yet the mechanism governing pericyte degeneration is poorly understood. Circular RNAs (circRNAs) play important roles in multiple biological processes and disease progression. Here, we investigated the role of circRNA in pericyte biology and diabetes-induced retinal vascular dysfunction. cZNF532 expression was upregulated in pericytes under diabetic stress, in the retinal vessels of a diabetic murine model, and in the vitreous humor of diabetic patients. cZNF532 silencing reduced the viability, proliferation, and differentiation of pericytes and suppressed the recruitment of pericytes toward endothelial cells in vitro. cZNF532 regulated pericyte biology by acting as a miR-29a-3p sponge and inducing increased expression of NG2, LOXL2, and CDK2. Knockdown of cZNF532 or overexpression of miR-29a-3p aggravated streptozotocin-induced retinal pericyte degeneration and vascular dysfunction. By contrast, overexpression of cZNF532 or inhibition of miR-29a-3p ameliorated human diabetic vitreous-induced retinal pericyte degeneration and vascular dysfunction. Collectively, these data identify a circRNA-mediated mechanism that coordinates pericyte biology and vascular homeostasis in DR. Induction of cZNF532 or antagonism of miR-29a-3p is an exploitable therapeutic approach for the treatment of DR.

• Publisher: American Society for Clinical Investigation
• Subject: Analysis / Animal models / Animals / Antibodies / Binding sites / Biology / Biomedical research / Blindness / Blood vessels / Cell cycle / Cell Line / Circular RNA / Cyclin-dependent kinase 2 / Datasets / Degeneration / Diabetes / Diabetes mellitus / Diabetic retinopathy / Diabetic Retinopathy - genetics / Diabetic Retinopathy - metabolism / Diabetic Retinopathy - pathology / Endothelial cells / Eye Proteins - genetics / Eye Proteins - metabolism / Gene expression / Glucose / Growth factors / Homeostasis / Humans / Mice / MicroRNAs - genetics / MicroRNAs - metabolism / Oxidative stress / Pericytes / Pericytes - metabolism / Pericytes - pathology / Physiological aspects / Retina / Retinal Vessels - metabolism / Retinal Vessels - pathology / Retinopathy / Ribonucleic acid / RNA / RNA, Circular - genetics / RNA, Circular - metabolism / Streptozocin / Variance analysis / Vitreous humor