Xindan Xing1, Hanying Wang1, Yuan Zhang1, Tian Niu1, Yan Jiang1, Xin Shi1, Chingyi Wang1, Kun Liu2. 1. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, 200080, China. 2. Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, 200080, China. Electronic address: drliukun@sjtu.edu.cn.
Abstract
PURPOSE: Angiogenesis is an essential part of the diabetes retinopathy (DR) process, and Zinc Finger RNA Binding Protein (ZFR) is important for vascularization to occur. However, the function and regulation of ZFR in DR development are not well understood. We hypothesized that high glucose condition could result in ZFR up-regulation in human retinal microvascular endothelial cells (HRMECs), thus contributing to disease progression, and O-glycosylation may be participated in this regulation. METHODS: Retinas were harvested from streptozotocin (STZ)-induced rat model of diabetes. Human umbilical vein endothelial cells (HUVECs) and HRMECs cultured in high glucose concentration, and retinal tissues were detected for ZFR expression. We examined the role of ZFR on vasculogenic processes including proliferation and migration in the cell model of DR. The effect of O-glycosylation modification on ZFR was further assessed in HRMECs. RESULTS: Expression of ZFR was up-regulated in high glucose condition both in vitro and in vivo. ZFR induced proliferation and migration of HRMECs. Inhibition of O-glycosylation modification attenuated the expression of ZFR. CONCLUSION: ZFR plays an important role in the pathogenesis of DR, and its mechanism may through the modification of O-glycosylation. Our research suggests that ZFR may be used as a potential prognostic marker or potential therapeutic target for DR.
PURPOSE: Angiogenesis is an essential part of the diabetes retinopathy (DR) process, and Zinc Finger RNA Binding Protein (ZFR) is important for vascularization to occur. However, the function and regulation of ZFR in DR development are not well understood. We hypothesized that high glucose condition could result in ZFR up-regulation in human retinal microvascular endothelial cells (HRMECs), thus contributing to disease progression, and O-glycosylation may be participated in this regulation. METHODS: Retinas were harvested from streptozotocin (STZ)-induced rat model of diabetes. Human umbilical vein endothelial cells (HUVECs) and HRMECs cultured in high glucose concentration, and retinal tissues were detected for ZFR expression. We examined the role of ZFR on vasculogenic processes including proliferation and migration in the cell model of DR. The effect of O-glycosylation modification on ZFR was further assessed in HRMECs. RESULTS: Expression of ZFR was up-regulated in high glucose condition both in vitro and in vivo. ZFR induced proliferation and migration of HRMECs. Inhibition of O-glycosylation modification attenuated the expression of ZFR. CONCLUSION:ZFR plays an important role in the pathogenesis of DR, and its mechanism may through the modification of O-glycosylation. Our research suggests that ZFR may be used as a potential prognostic marker or potential therapeutic target for DR.