microRNA-29b-3p attenuates diabetic nephropathy in mice by modifying EZH2
Yurong Zhao1, Dandan Li1, Ping Zhou2
1Department of Endocrinology, the Fourth People's Hospital of Shenyang, Shenyang, 110000, Liaoning, China.
Objective:
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease around the world. This study investigated the role of microRNA (miR)-29b-3p in DN and the mechanism of the miR-29b-3p/EZH2 axis in DN.
Methods:
Peripheral blood samples of DN patients were collected and miR-29b-3p and EZH2 expression levels were evaluated using RT-qPCR. DN mouse models were successfully established, and then treated with miR-29b-3p overexpression or EZH2 silence. IL-1β, IL-6, and TNF-α levels were assessed by ELISA. Blood glucose, serum creatinine (Scr), 24-h urine volume, 24-h urine protein, and blood urea nitrogen (BUN) levels were examined by automatic biochemical analyzer detection. HE staining was performed to observe the renal histopathology, and TUNEL staining was implemented to test apoptosis in renal tissues. The binding relationship between miR-29b-3p and EZH2 was validated by using a bioinformatics website and dual luciferase reporter gene assay.
Results:
miR-29b-3p was lowly expressed, and EZH2 was highly expressed in patients with DN. Overexpressing miR-29b-3p or silencing EZH2 attenuated renal dysfunction, suppressed inflammation and apoptosis, and relieved renal injuries in mice with DN. miR-29b-3p inhibited EZH2, and miR-29b-3p overexpression mitigated renal injuries in DN mice by repressing EZH2.
Conclusion:
miR-29b-3p suppresses EZH2 expression thereby inhibiting the progression of DN in mice.
Insights
MicroRNA-29b-3p is downregulated in diabetic nephropathy (DN). Restoring miR-29b-3p levels inhibits EZH2, reducing kidney damage and inflammation in DN mouse models.
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Diabetic nephropathy (DN) is a primary cause of end-stage renal disease globally.
- Understanding the molecular mechanisms underlying DN progression is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of microRNA (miR)-29b-3p in diabetic nephropathy.
- To elucidate the mechanism of the miR-29b-3p/EZH2 axis in DN pathogenesis.
Main Methods:
- Assessed miR-29b-3p and EZH2 expression in DN patients' blood using RT-qPCR.
- Utilized DN mouse models with miR-29b-3p overexpression or EZH2 silencing.
- Measured inflammatory markers (IL-1β, IL-6, TNF-α), renal function indicators, and performed histopathological and apoptosis analyses.
- Validated miR-29b-3p and EZH2 interaction via bioinformatics and dual luciferase reporter assays.
Main Results:
- DN patients exhibited low miR-29b-3p and high EZH2 expression.
- miR-29b-3p overexpression or EZH2 silencing ameliorated renal dysfunction, inflammation, and apoptosis in DN mice.
- miR-29b-3p directly inhibits EZH2, and this repression mitigates renal injury in DN.
Conclusions:
- miR-29b-3p acts as a suppressor of EZH2 expression.
- Targeting the miR-29b-3p/EZH2 pathway holds therapeutic potential for inhibiting diabetic nephropathy progression.
