Egr1 mediates retinal vascular dysfunction in diabetes mellitus via promoting p53 transcription

被引：43
作者：
Ao, Haocheng [1 ]
Liu, Bingqian [1 ]
Li, Haichun [1 ]
Lu, Lin [1 ]
机构：
[1] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou, Guangdong, Peoples R China
来源：
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE | 2019年 / 23卷 / 05期
基金：
中国国家自然科学基金;
关键词：
diabetic retinopathy; Egr1; p53; TUMOR-SUPPRESSOR; TISSUE FACTOR; EXPRESSION; HYPERGLYCEMIA; PROTEIN; CELLS; ACTIVATION; APOPTOSIS; INSULIN; GLUCOSE;
D O I：
10.1111/jcmm.14225
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Objectives: This study focused on investigating the expression and underlying molecular mechanism of early growth response 1(Egr1) in diabetic retinopathy. Methods: A microarray assay was applied to examine differentially expressed genes in the retina tissues of normal rats, as well as in those of streptozotocin-induced diabetic rats. Human retinal vascular endothelial cells (HRVECs) transfected with sh-NC, sh-Egr1 or sh-Egr1+ pVax1-p53 were cultured under high-glucose conditions and then used to explore the role of Egr1 in vitro. The effect of Egr1 on retinal vascular dysfunction caused by diabetes was examined by sh-Egr1 administration in vivo. Results: Early growth response 1 was found to be up-regulated in the retinas of diabetic rats compared to those of normal rats. Down-regulation of Egr1 in HRVECs under high-glucose conditions inhibited the apoptosis, migration and tube formation in vitro. Moreover, sh-Egr1 partially reduced the injurious effects of hyperglycaemia on retinal vascular function by decreasing apoptotic cells and microvascular formation in vivo. The reduction of Egr1 evidently down-regulated the p53 expression. Overexpression of p53 rescued the inhibition of sh-Egr1in HRVECs under high-glucose concentration on apoptosis, migration and tube formation in vitro. Conclusion: Down-regulation of Egr1 partially reduced the injurious effects of hyper-glycaemia on retinal vascular function via inhibiting p53 expression.
引用
收藏
页码：3345 / 3356
页数：12
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