Huang Yu-Chuen, Liao Wen-Ling, Lin Jane-Ming, Chen Ching-Chu, Liu Shih-Ping, Chen Shih-Yin, Lin Yu-Ning, Lei Yu-Jie, Liu Huan-Ting, Chen Yu-Jen, Tsai Fuu-Jen
Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan.
School of Chinese Medicine, China Medical University, Taichung 404, Taiwan.
Oncotarget. 2018 Apr 3;9(25):17858-17866. doi: 10.18632/oncotarget.24909.
Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Circulating endothelial progenitor cells (EPCs) are derived from bone marrow and are characterized by pathological retinal neovascularization. () is a DR susceptibility gene that interacts with its downstream regulatory protein ras-related C3 botulinum toxin substrate 1 (Rac1), to assist in endothelial cell angiogenesis and increasing capillary permeability. The aim of this study was to elucidate the relationship between ARHGAP22 expression and EPC levels in type 2 diabetes (T2D) patients with DR. Fifty T2D patients with DR were recruited. Circulating EPCs were characterized as CD31/vascular endothelial growth factor-2/CD45/CD133 and were quantified using triple staining flow cytometry. Real-time polymerase chain reaction tests were used to quantify ARHGAP22 expression. We found that T2D patients with proliferative DR had significantly lower EPC levels than those with non-proliferative DR ( = 0.028). T2D patients with EPC levels above the median value (> 4 cells/10 events) had higher levels of ARHGAP22 expression ( = 0.002). EPC levels were positively correlated with ARHGAP22 expression ( = 0.364, = 0.009). Among T2D patients with DR, a higher expression of ARHGAP22 was associated with higher levels of EPCs. ARHGAP22 may be involved in the mobilization or active circulation of EPCs, thus contributing to neovascularization during DR development.
糖尿病视网膜病变（DR）是糖尿病常见的微血管并发症。循环内皮祖细胞（EPCs）来源于骨髓，其特征为病理性视网膜新生血管形成。（）是一种DR易感基因，它与其下游调节蛋白Ras相关C3肉毒杆菌毒素底物1（Rac1）相互作用，以协助内皮细胞血管生成并增加毛细血管通透性。本研究的目的是阐明2型糖尿病（T2D）合并DR患者中ARHGAP22表达与EPC水平之间的关系。招募了50例T2D合并DR的患者。循环EPCs被鉴定为CD31/血管内皮生长因子-2/CD45/CD133，并使用三重染色流式细胞术进行定量。采用实时聚合酶链反应试验定量ARHGAP22的表达。我们发现，增殖性DR的T2D患者的EPC水平显著低于非增殖性DR患者（=0.028）。EPC水平高于中位数（>4个细胞/10⁶事件）的T2D患者的ARHGAP22表达水平更高（=0.002）。EPC水平与ARHGAP22表达呈正相关（=0.364，=0.009）。在T2D合并DR的患者中，ARHGAP22的高表达与EPCs水平升高有关。ARHGAP22可能参与EPCs的动员或活跃循环，从而在DR发展过程中促进新生血管形成。
