Han Li1, Feng Zhou1, Xingjian Cao1, Ping Zhao1, Xiaobo Huang2, Wei Xie1, Guowei Zhang3, Xiang Chen4. 1. Department of Clinical Laboratory, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. 2. Department of Ophthalmology, The Second Affiliated Hospital of Nantong University, Nantong, China. 3. Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. zgweyelab@163.com. 4. Department of Clinical Laboratory, The Second Affiliated Hospital of Nantong University, Nantong, Jiangsu, China. ntchenx0520@163.com.
Abstract
PURPOSE: The proliferation and angiogenesis of human retinal endothelial cells (HRECs) are critical for the pathophysiology of diabetic retinopathy (DR). C-terminal binding protein 2 (CtBP2) has multiple biologic functions, but its effect on HRECs under high-glucose (HG) conditions is unclear. METHODS: The cell viability, angiogenesis, cellular adhesion and CtBP2 expression levels of HRECs were measured following treatment with different concentrations of glucose. Small interfering CtBP2-targeting RNA, wide-type and function mutant plasmid of CtBP2 were constructed and then were transfected into HRECs to evaluate the effects of CtBP2 on cell functions of HRECs. RESULTS: The expression of CtBP2 in HRECs was increased after HG treatment. HG treatment significantly increased cell proliferation, angiogenesis, and decreased relative gene expressions in gap junctions, tight junctions and adherens junctions. After CtBP2 was inhibited via siRNA, the changes induced by HG were partially restored. Conversely, only wild-type CtBP2 could increase cell proliferation and angiogenesis under HG condition. Mechanistically, we also found that CtBP2 exerted its functions to effect HG-induced changes via Akt signaling pathway. CONCLUSION: This study implicates that CtBP2 promotes HG-induced cell proliferation, angiogenesis and cellular adhesion, and CtBP2 might be a potential target in the prevention of DR.
PURPOSE: The proliferation and angiogenesis of human retinal endothelial cells (HRECs) are critical for the pathophysiology of diabetic retinopathy (DR). C-terminal binding protein 2 (CtBP2) has multiple biologic functions, but its effect on HRECs under high-glucose (HG) conditions is unclear. METHODS: The cell viability, angiogenesis, cellular adhesion and CtBP2 expression levels of HRECs were measured following treatment with different concentrations of glucose. Small interfering CtBP2-targeting RNA, wide-type and function mutant plasmid of CtBP2 were constructed and then were transfected into HRECs to evaluate the effects of CtBP2 on cell functions of HRECs. RESULTS: The expression of CtBP2 in HRECs was increased after HG treatment. HG treatment significantly increased cell proliferation, angiogenesis, and decreased relative gene expressions in gap junctions, tight junctions and adherens junctions. After CtBP2 was inhibited via siRNA, the changes induced by HG were partially restored. Conversely, only wild-type CtBP2 could increase cell proliferation and angiogenesis under HG condition. Mechanistically, we also found that CtBP2 exerted its functions to effect HG-induced changes via Akt signaling pathway. CONCLUSION: This study implicates that CtBP2 promotes HG-induced cell proliferation, angiogenesis and cellular adhesion, and CtBP2 might be a potential target in the prevention of DR.
Authors: Antonia M Joussen; Vassiliki Poulaki; Akitaka Tsujikawa; Wenying Qin; Tamim Qaum; Qingwen Xu; Yasufumi Moromizato; Sven-Erik Bursell; Stanley J Wiegand; John Rudge; Ella Ioffe; George D Yancopoulos; Anthony P Adamis Journal: Am J Pathol Date: 2002-05 Impact factor: 4.307
Authors: Y Zhang; X Jiang; X Qin; D Ye; Z Yi; M Liu; O Bai; W Liu; X Xie; Z Wang; J Fang; Y Chen Journal: Oncogene Date: 2010-07-05 Impact factor: 9.867