Ogg1 regulates TGF‑β-Smad3 signalling and fibrosis progression in chronic kidney disease

  • Commun Biol. 2026 May 11. doi: 10.1038/s42003-026-10177-0.
Ying Wang  1  2  3 ,  Yan Liu  1  2 ,  Bo Peng  4 ,  Chan Zou  5 ,  Guoping Yang  5  6 ,  Jiefu Zhu  7 ,  Hao Zhang  8  9 ,  Jing Huang  10
Affiliations
  • 1. Department of Nephrology, The Third Xiangya Hospital at Central South University, Changsha, China.
  • 2. Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China.
  • 3. Postdoctoral Station of Pharmacy, the Third Xiangya Hospital, Central South University, Changsha, China.
  • 4. Transplantation Center, The Third Xiangya Hospital, Central South University, Changsha, China.
  • 5. Center for Clinical Pharmacology, the Third Xiangya Hospital, Central South University, Changsha, China.
  • 6. Xiangya School of Pharmaceutical Science, Central South University, Changsha, China.
  • 7. Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, China. [email protected].
  • 8. Department of Nephrology, The Third Xiangya Hospital at Central South University, Changsha, China. [email protected].
  • 9. Clinical Research Center for Critical Kidney Disease in Hunan Province, Changsha, China. [email protected].
  • 10. Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China. [email protected].
PMID: 42115320 DOI: 10.1038/s42003-026-10177-0
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.

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