Abstract
The present study explored the effect of miR-200b on the development of diabetic retinopathy (DR) by targeting vascular endothelial growth factor A (VEGFA) gene. The study populations consisted of 255 DR patients (case group) and 253 healthy people (control group), while the expressions of miR-200b and VEGFA mRNA were detected by quantitative real-time PCR (qRT-PCR). Bioinformatics software and dual-luciferase reporter assay were used to confirm VEGFA as a target gene of miR-200b. Also, a total of 70 Wistar male rats were selected and randomly assigned into blank, normal control (NC), miR-200b mimics, miR-200b inhibitors, miR-200b inhibitors + silencing vascular endothelial growth factor A (siVEGFA), and siVEGFA groups (n=10/group) respectively. Streptozotocin (STZ)-induced rat models of DR were successfully established. VEGFA, transforming growth factor-β1 (TGF-β1), hepatocyte growth factor (HGF), and pigment epithelium-derived factor (PEDF) were detected using qRT-PCR and Western blotting. In comparison with the control group, the case group showed lower expression of miR-200b but higher expression of VEGFA mRNA. VEGFA was confirmed as a target gene of miR-200b. Rats in the miR-200b mimics and siVEGFA groups exhibited higher expression of PEDF mRNA and protein but lower expressions of VEGFA, TGF-β1, HGF protein, and mRNA than the NC group. There was no remarkable difference in expressions of PEDF, VEGFA, TGF-β1, HGF protein, and mRNA between the miR-200b inhibitors + siVEGFA and NC groups. In conclusion, the present study demonstrated that miR-200b might alleviate DR development by down-regulating its target gene VEGFA.
Highlights
Diabetic retinopathy (DR) is a sight-threatening chronic complication that virtually harms patients with diabetes [1]
Compared with healthy people in the control group, patients with DR in the case group significantly decreased in miR-200b expression and significantly increased in vascular endothelial growth factor A (VEGFA) mRNA expression (P
Rats in the miR-200b inhibitors group were increased in the expressions of VEGFA, transforming growth factor-β1 (TGF-β1), and hepatocyte growth factor (HGF) proteins, but decreased in the expression of pigment epithelium-derived factor (PEDF) protein. These results suggested that miR-200b over-expression and VEGFA low-expression can reduce the expression of retinopathy-related proteins such as TGF-β1 and HGF, while enhance the expression of PEDF protein
Summary
Diabetic retinopathy (DR) is a sight-threatening chronic complication that virtually harms patients with diabetes [1]. Patients with DR exhibited increased oxidative stress in diabetes, higher superoxide levels and damaged antioxidant defense systems in the retina and the capillary cells [3]. It is characterized by progressive alterations in the retinal microvasculature, causing increased vasopermeability, non-perfusion retinal areas and pathologic intraocular proliferation of retinal vessels responding to retinal non-perfusion [1]. With the increasingly pandemic diabetes, new approaches are eagerly needed to understand the pathophysiology and to enhance the prevention, detection, and treatment of DR [4]. An all-round understanding of the molecular and biochemical changes in DR at early stage may be conducive to new and effective therapy methods for DR prevention and amelioration [5]
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