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

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-Egr1 in HRVECs under high-glucose concentration on apoptosis, migration and tube formation in vitro. CONCLUSION:Down-regulation of Egr1 partially reduced the injurious effects of hyperglycaemia on retinal vascular function via inhibiting p53 expression.

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