The role of endoplasmic reticulum stress in the early stage of diabetic retinopathy
The role of endoplasmic reticulum stress in the early stage of diabetic retinopathy
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内质网应激在糖尿病视网膜病变早期的作用
DOI：
10.1007/s00592-009-0170-z
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发表时间：
2011-06-01
影响因子：
3.8
通讯作者：
Zhao, Min Hong
中科院分区：
文献类型：
--
作者：
Li, Bin;Wang, Hong Sheng;Zhao, Min Hong
本研究的目的是通过体外和体内模型评估内质网（ER）应激在糖尿病视网膜病变（DR）中的作用。在体内研究中，在大鼠中诱导糖尿病，并在1、3和6个月时评估各组大鼠视网膜中葡萄糖调节蛋白78 （GRP78）、激活转录因子4 （ATF4）、C/EBP同源蛋白（CHOP）和血管内皮生长因子（VEGF）的表达。在体外研究中，我们在不同葡萄糖浓度下培养人视网膜毛细血管内皮细胞（HRCECs），并评估GRP78、ATF4、CHOP和VEGF mRNA和蛋白的表达。所选择的葡萄糖浓度反映了糖尿病患者的明显浓度。1、3、6个月时，糖尿病大鼠VEGF和CHOP mRNA的表达水平较对照组显著升高（P < 0.05）。在高和可变葡萄糖浓度培养的HRCECs中，CHOP表达和凋亡显著增加（P < 0.05）。而GRP78和ATF4的表达水平没有变化。我们的研究结果表明DR的早期进展可能是由内质网应激介导的，但可能不涉及ATF4或GRP78的变化。
The aim of this study was to evaluate the role of endoplasmic reticulum (ER) stress in diabetic retinopathy (DR) using in vitro and in vivo models. For the in vivo studies, diabetes was induced in rats, and retinal expression of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and vascular endothelial growth factor (VEGF) in groups of rats at 1, 3, and 6 months was assessed. For the in vitro studies, human retinal capillary endothelial cells (HRCECs) were cultured in the presence of varying glucose concentrations, and the expression of mRNA and protein for GRP78, ATF4, CHOP, and VEGF was assessed. The chosen glucose concentrations were reflective of those apparent in diabetic patients. Expression of VEGF and CHOP mRNA levels were significantly increased in diabetic rats compared to control rats at 1, 3, and 6 months (P < 0.05). In HRCECs cultured in the presence of high as well as variable glucose concentrations, CHOP expression and apoptosis were significantly increased (P < 0.05). However, GRP78 and ATF4 expression levels were unchanged. Our findings suggest that early progression of DR may be mediated by ER stress, but probably does not involve changes in ATF4 or GRP78.