miR-205-5p ameliorates podocyte injury in diabetic nephropathy by targeting vascular endothelial growth factor A
Yingdan Zhao1, Yunhai Tang1, Qingqing Wang1
1Department of Nephrology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai City, China.
Abstract:
ObjectiveThis work aims to elucidate the effect and the regulatory mechanisms of miR-205-5p on podocyte injury and oxidative stress in diabetic nephropathy.MethodsA mouse model of diabetic nephropathy was established. Fasting blood glucose, 24 hours urinary albumin, serum creatinine and blood urea nitrogen of mice were detected. H&E and Tunel staining of mice renal tissues were executed to detect histological changes and apoptosis. A cell model of diabetic nephropathy was constructed by inducing mouse podocytes with high glucose. The function of miR-205-5p on viability, apoptosis, and levels of malondialdehyde, superoxide dismutase and glutathione in the diabetic nephropathy cell model was evaluated by CCK-8 assay, Tunel staining and enzyme-linked immunosorbent assay. Binding of miR-205-5p and vascular endothelial growth factor A was verified by dual luciferase reporter gene assay. Rescue experiment was implemented on the diabetic nephropathy cell model to research whether miR-205-5p regulated diabetic nephropathy development by targeting vascular endothelial growth factor A. Quantitative reverse transcription-polymerase chain reaction and Western blot were for the detection of gene expression.ResultsThe increased fasting blood glucose, 24 hours urinary albumin, serum creatinine and blood urea nitrogen levels, the intensified apoptosis and injury, and the down-regulated miR-205-5p were observed in renal tissues. miR-205-5p relieved podocyte injury in diabetic nephropathy, as it increased cell viability, decreased cell apoptosis, reduced malondialdehyde, and elevated superoxide dismutase and glutathione in the diabetic nephropathy cell model. Vascular endothelial growth factor A was up-regulated in renal tissues of diabetic nephropathy mice, and directly suppressed by miR-205-5p. Vascular endothelial growth factor A up-regulation abolished the protection of miR-205-5p on the diabetic nephropathy cell model.ConclusionsmiR-205-5p might relieve podocyte injury in diabetic nephropathy by suppressing Vascular endothelial growth factor A. It might be a promising target for diabetic nephropathy treatment.
Insights
MicroRNA-205-5p alleviates diabetic nephropathy by reducing podocyte injury and oxidative stress. It achieves this by suppressing Vascular Endothelial Growth Factor A, offering a potential new treatment target.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Diabetic nephropathy (DN) is a major complication of diabetes, characterized by podocyte injury and oxidative stress.
- MicroRNAs (miRNAs) play crucial roles in regulating cellular processes and have emerged as potential therapeutic targets in DN.
Purpose of the Study:
- To investigate the role and regulatory mechanisms of miR-205-5p in podocyte injury and oxidative stress in diabetic nephropathy.
- To determine if miR-205-5p targets Vascular Endothelial Growth Factor A (VEGF-A) in the context of DN.
Main Methods:
- Established mouse and cell models of diabetic nephropathy.
- Assessed kidney function markers, histological changes, and apoptosis.
- Quantified miR-205-5p, VEGF-A, oxidative stress markers (malondialdehyde, superoxide dismutase, glutathione), cell viability, and apoptosis.
- Utilized dual luciferase reporter gene assays and rescue experiments to confirm target interaction and functional significance.
Main Results:
- Diabetic nephropathy mice exhibited elevated blood glucose, albuminuria, creatinine, BUN, renal injury, apoptosis, and decreased miR-205-5p.
- miR-205-5p overexpression protected podocytes by increasing viability, reducing apoptosis, and improving oxidative stress markers.
- VEGF-A was upregulated in DN and directly suppressed by miR-205-5p.
- VEGF-A upregulation reversed the protective effects of miR-205-5p in podocytes.
Conclusions:
- miR-205-5p ameliorates podocyte injury and oxidative stress in diabetic nephropathy.
- The protective mechanism involves the suppression of VEGF-A.
- miR-205-5p represents a promising therapeutic target for diabetic nephropathy.
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