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. 2023 Jun;22(2):223-233.
doi: 10.1007/s42000-022-00426-2. Epub 2023 Jan 24.

microRNA-29b-3p attenuates diabetic nephropathy in mice by modifying EZH2

Yurong Zhao  1 , Dandan Li  1 , Ping Zhou  2 , Yujie Zhao  3 , Jinsong Kuang  4
Affiliations

microRNA-29b-3p attenuates diabetic nephropathy in mice by modifying EZH2

Yurong Zhao et al. Hormones (Athens). 2023 Jun.

Abstract

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.

Keywords: Apoptosis; Diabetic nephropathy; Enhancer of zeste homolog 2; Inflammatory response; MicroRNA-29b-3p.

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