Abstract
Kidney fibrosis is a hallmark of chronic kidney disease (CKD) and a major contributor to progression toward end-stage renal disease. Here, we identify 8-oxoguanine DNA glycosylase 1 (Ogg1), a DNA repair enzyme, as a regulator of kidney fibrosis. Ogg1 expression is upregulated in experimental fibrosis models in male mice, including unilateral ureteral obstruction (UUO) and aristolochic acid (AA) nephropathy, as well as in kidney tissues from CKD patients. Genetic deletion of Ogg1 reduces fibrosis, tubular atrophy and fibrotic marker expression, and improves renal function in AA nephropathy. Mechanistically, Ogg1 interacts with phosphorylated Smad3 in the nucleus and promotes transcriptional regulation of profibrotic genes. Pharmacological inhibition of Ogg1 with TH5487 alleviates fibrosis in both UUO and AA nephropathy models, supporting Ogg1 as a potential therapeutic target in CKD.
Similar content being viewed by others
Acknowledgements
This study was supported by the National Natural Science Foundation of China (Grant No. 82400809); the 1st China Postdoctoral Science Foundation–Hunan Province Joint Fund (Special Grant) (Grant No. 2025T027HN); the Hubei Provincial Health Commission Health Science and Technology Program (Grant No. WJ2025Q017); the National Funding Program for Postdoctoral Researchers (Category C) (Grant No. GZC20251489); and the 77th China Postdoctoral Science Foundation (General Program) (Grant No. 2025M772282).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Wang, Y., Liu, Y., Peng, B. et al. Ogg1 regulates TGF‑β–Smad3 signalling and fibrosis progression in chronic kidney disease. Commun Biol (2026). https://doi.org/10.1038/s42003-026-10177-0
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s42003-026-10177-0
