VE钙粘蛋白
血-视网膜屏障
血管内皮生长因子
促红细胞生成素
脐静脉
内分泌学
内科学
医学
内化
异硫氰酸荧光素
促红细胞生成素受体
糖尿病性视网膜病变
化学
受体
内皮干细胞
糖尿病
体外
生物化学
血管内皮生长因子受体
物理
荧光
量子力学
作者
Dandan Liu,Hua Xu,Chaoyang Zhang,Hai Xie,Qian Yang,Weiye Li,Haibin Tian,Lixia Lü,Jingying Xu,Guoxu Xu,Kun Liu,Xiaodong Sun,Guo‐Tong Xu,Jingfa Zhang
出处
期刊:Life Sciences
[Elsevier]
日期:2020-10-01
卷期号:259: 118273-118273
被引量:17
标识
DOI:10.1016/j.lfs.2020.118273
摘要
To explore the mechanisms of erythropoietin (EPO)'s protection on inner blood-retinal barrier (iBRB) in experimental diabetic retinopathy. Male SD rats were rendered diabetic with streptozotocin, followed by intravitreal injection of EPO. The permeability of iBRB was examined with fluorescein isothiocyanate (FITC)-dextran. Human retinal microvascular endothelial cells (HRMECs) and human umbilical vein endothelial cells (HUVECs) were treated with glyoxal and studied for cell viability and barrier function. The expressions of vascular endothelial (VE)-cadherin, Src kinase, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) were analyzed with Western blot, ELISA, qPCR, or immunofluorescence. VE-cadherin in rat retinas was down-regulated with diabetes progression. EPO treatment could increase VE-cadherin expression at week 8 and week 16. The expressions of p-Src and p-VE-cadherin were increased at week 2, while decreased at week 8 of diabetes; which were prevented by EPO. The leakage of FITC-dextran in 8-week diabetic rat retinas was ameliorated by EPO. In vitro results showed the expressions of VEGF, p-Src and p-VE-cadherin were increased significantly, accompanied with the decreased barrier function, which were prevented by EPO. Ranibizumab and CGP77675 also inhibited the glyoxal-induced phosphorylation of Src and VE-cadherin. Cellular fractionation showed EPO mitigated the VE-cadherin internalization in glyoxal-treated cells. EPO maintained the expression of VE-cadherin in experimental diabetic retinopathy by inhibiting its phosphorylation and internalization through VEGF/VEGFR2/Src pathway, thus improved the integrity of iBRB.
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