Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Apr 15, 2025; 16(4): 93630
Published online Apr 15, 2025. doi: 10.4239/wjd.v16.i4.93630
MiR-29a-3p inhibits fibrosis of diabetic kidney disease in diabetic mice via downregulation of DNA methyl transferase 3A and 3B
Ying Yang, Yi Chen, Jian-Ying Tang, Jian Chen, Gui-Qing Li, Bing Feng, Jiao Mu
Ying Yang, Yi Chen, Jian-Ying Tang, Department of Nephrology, University-Town Hospital of Chongqing Medical University, Chongqing 401331, China
Jian Chen, Gui-Qing Li, Institute of Immunology, The Third Military Medical University, Chongqing 400038, China
Bing Feng, Department of Nephrology, Third Military Medical University, Chongqing 400038, China
Jiao Mu, Department of Nephrology, Chongqing Medical University, Chongqing 401331, China
Co-first authors: Ying Yang and Yi Chen.
Co-corresponding authors: Bing Feng and Jiao Mu.
Author contributions: Yang Y and Chen Y contributed to the design of the study, acquiring and analyzing data from experiments, and writing of the manuscript and jointly wrote this manuscript; Chen J, Li GQ, Tang JY, and Feng B provided suggestions on the design of the experiment and the interpretation of the results; Mu J, Feng B, Yang Y, and Chen Y conceived the project; Mu J and Feng B received funding for the project; Mu J is the guarantor of this work; All authors commented and edited the manuscript and approved the final version.
Supported by the Chongqing Basic Research and Frontier Exploration Project, No. cstc2018jcyjAX0834.
Institutional review board statement: After examination by the Hospital Ethics Committee, the research plan and other materials submitted in this project conform to the principles of medical ethics and the requirements of Helsinki Declaration.
Institutional animal care and use committee statement: The experiment met the ethical standards of animal experimental research. All animals were reviewed and approved by the Ethics Committee of University-town Hospital of Chongqing Medical University, No. LL-202125.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: Data available on request due to restrictions privacy or ethical. The data presented in this study are available on request from the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jiao Mu, Doctor, Department of Nephrology, Chongqing Medical University, No. 55 University City Road, Chongqing 401331, China. 800273@cqmu.edu.cn
Received: March 2, 2024
Revised: September 16, 2024
Accepted: January 20, 2025
Published online: April 15, 2025
Processing time: 362 Days and 22.2 Hours
Abstract
BACKGROUND

At present, the incidence of diabetic nephropathy is increasing year by year, and there are many studies on the pathogenesis of diabetic nephropathy, but it is still not completely clear. The final pathological result of diabetic nephropathy is mainly glomerular cell fibrosis, and the roles of micro-RNA (miRNA)-29 and DNA methyl transferase (DNMTs) in cell fibrosis have been confirmed in other studies, but there is a lack of relevant research in the kidney at present.

AIM

To study the potential involvement of miRNA-29a-3p in fibrosis related to diabetic kidney disease (DKD).

METHODS

The expression of miR-29a-3p, DNMT3A/3B, fibrosis-related molecules, Wnt3a, β-catenin, Janus kinase 2, and signal transducer and activator of transcription 3 was assessed in SV40MES13 cells and diabetic mice using quantitative real-time PCR and western blotting. Furthermore, the expression changes of fibrosis-related molecules were further analyzed using immunofluorescence and immunohistochemical blotting. The renal pathological changes of DKD in each group were also studied using hematoxylin-eosin and periodate-Schiff reaction staining.

RESULTS

In both the in vivo and in vitro experiments, it was observed that high glucose induction significantly decreased miR-29a-3p expression. As a result of this downregulation, DKD-related fibrosis was found to be promoted, as confirmed by elevated expression levels of α-smooth muscle actin, collagen type I, and fibronectin. MiR-29a-3p targets the 3’ non-coding regions of DNMT3A and DNMT3B and inhibits their expression. Inhibition of DNMT3A and DNMT3B can reverse the effect of miR-29a-3p downregulation on DKD-related fibrosis.

CONCLUSION

MiR-29a-3p can regulate Wnt/β-catenin and Janus kinase/signal transducer and activator of transcription signal pathways by regulating and inhibiting the expression of DNMT3A/3B and thus participate in the inhibition of DKD-related fibrosis.

Keywords: Diabetic kidney disease; Mir-29a-3p; DNA methylation; Janus kinase/signal transducer and activator of transcription; Wnt/β-catenin; Renal fibrosis

Core Tip: This study was the first to verify that MiR-29a-3p can regulate Wnt/β-catenin and Janus kinase/signal transducer and activator of transcription signal pathways by regulating and inhibiting the expression of DNMT3A/3B and thus participate in the inhibition of diabetic kidney disease-related fibrosis by in vitro and in vivo experiments. These findings indicated that targeting miR-29a-3p and DNMT3A/3B may hold promise for diabetic kidney disease prevention and treatment.