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MiR-770-5p facilitates podocyte apoptosis and inflammation in diabetic nephropathy by targeting TIMP3
1Department of Geriatrics, Xiangyang NO. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei, China.
Objective:
Diabetic nephropathy (DN) is one of the most severe and frequent diabetic complications. MicroRNAs (miRNAs) have been reported to play a vital role in DN pathogenesis. The present study aimed to investigate the molecular mechanism of miR-770-5p in DN.
Methods:
Podocyte injury model was established by treating mouse podocytes with high glucose (HG, 33 mM) for 24 h. The levels of miR-770-5p and TIMP3 were examined in kidney tissues and podocytes using quantitative real-time PCR (qRT-PCR). Flow cytometry analysis was applied to detect apoptosis in podocytes. Western blot assay was used to measure the protein levels of B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X (Bax) and tissue inhibitors of metalloproteinase 3 (TIMP3). Enzyme-linked immunosorbent assay (ELISA) was conducted to measure the levels of inflammatory factors. The interaction between miR-770-5p and TIMP3 was determined by MicroT-CDS and luciferase reporter assay.
Results:
MiR-770-5p was up-regulated and TIMP3 was down-regulated in DN kidney tissues and HG-stimulated podocytes. Depletion of miR-770-5p suppressed cell apoptosis and the release of pro-inflammatory factors in HG-treated podocytes. Additionally, TIMP3 was a target of miR-770-5p in HG-treated podocytes. TIMP3 inhibited cell apoptosis and inflammation in HG-treated podocytes. Moreover, TIMP3 knockdown alleviated the inhibitory effect of miR-770-5p silencing on podocyte apoptosis and inflammatory response.
Conclusion:
Knockdown of miR-770-5p suppressed podocyte apoptosis and inflammatory response by targeting TIMP3 in HG-treated podocytes, indicating that miR-770-5p may be a potential therapeutic target for DN therapy.
Insights
MicroRNA-770-5p (miR-770-5p) targets TIMP3, suppressing podocyte apoptosis and inflammation in diabetic nephropathy (DN). Silencing miR-770-5p offers a potential therapeutic strategy for DN.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Diabetic nephropathy (DN) is a severe complication of diabetes, involving microRNA (miRNA) dysregulation.
- Podocyte injury is a key factor in DN pathogenesis.
Purpose of the Study:
- To investigate the role and molecular mechanism of miR-770-5p in diabetic nephropathy.
- To explore miR-770-5p's potential as a therapeutic target for DN.
Main Methods:
- Established a high glucose-induced mouse podocyte injury model.
- Quantified miR-770-5p and TIMP3 levels using qRT-PCR.
- Assessed podocyte apoptosis via flow cytometry and Western blot.
- Measured inflammatory factors using ELISA.
- Validated miR-770-5p and TIMP3 interaction using luciferase reporter assay.
Main Results:
- miR-770-5p was upregulated, while TIMP3 was downregulated in DN kidney tissues and high glucose-treated podocytes.
- miR-770-5p depletion reduced podocyte apoptosis and inflammation.
- TIMP3, a target of miR-770-5p, inhibited apoptosis and inflammation.
- TIMP3 knockdown reversed the protective effects of miR-770-5p silencing.
Conclusions:
- miR-770-5p promotes podocyte apoptosis and inflammation in DN by targeting TIMP3.
- Targeting miR-770-5p represents a promising therapeutic approach for diabetic nephropathy.
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