Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2026 Jan;58(1):179-187.
doi: 10.1007/s11255-025-04651-7. Epub 2025 Jul 14.

Targeting the TFAM-cGAS-STING axis: a mitochondrial-inflammatory link in the pathogenesis and treatment of diabetic kidney disease

Jingting Yun  1 , Jinyi Shan  1 , Ji Li  2
Affiliations
Review

Targeting the TFAM-cGAS-STING axis: a mitochondrial-inflammatory link in the pathogenesis and treatment of diabetic kidney disease

Jingting Yun et al. Int Urol Nephrol. 2026 Jan.

Abstract

Diabetic kidney disease (DKD) is one of the common and devastating chronic complications of diabetes, its pathogenesis remains incompletely understood. Emerging evidence suggests that mitochondrial dysfunction plays a crucial role in the onset and progression of DKD. Mitochondrial transcription factor A (TFAM), a key regulator of mitochondrial DNA (mtDNA) expression, is essential for maintaining mitochondrial integrity and function, and is increasingly recognized for its role in modulating inflammatory signaling. This review focuses on the regulatory mechanisms by which TFAM stabilizes mitochondrial function and prevents mtDNA leakage, thereby inhibiting activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. Suppression of this pathway has been shown to alleviate renal inflammation and fibrosis. Given the current lack of curative therapies for DKD, targeting the TFAM-cGAS-STING signaling axis represents a promising novel strategy for both therapeutic intervention and mechanistic research in DKD.

Keywords: Diabetic kidney disease; Inflammation; Mitochondrial dysfunction; TFAM; cGAS–STING pathway.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval: Not applicable. Informed consent: Informed consent was obtained from all participants.

Figures

Fig. 1
Fig. 1
Mechanism of the TFAM-cGAS-STING Axis in DKD
See this image and copyright information in PMC

References

    1. Wang X, Deng Z, Wang Y (2025) IgG expressed by renal tubular epithelial cells in epithelial mesenchymal transformation and interstitial fibrosis in diabetic kidney disease. Ren Fail 47(1):2458764. 10.1080/0886022x.2025.2458764 - DOI - PMC - PubMed
    1. Zhou Y, Liu Y, Wu L, Zhang Y, Wen H, Hu J, Huo Z, Ju S, Sheng R (2025) Causal insights into major risk factors for diabetic kidney disease: a comprehensive meta-analysis and Mendelian randomization study. Ren Fail 47(1):2468741. 10.1080/0886022x.2025.2468741 - DOI - PMC - PubMed
    1. Sood A, Sawhney A, Borokhovsky B, Vyas AV, Gupta R (2025) A drug safety evaluation of dapagliflozin for diabetic nephropathies in patients with cardiovascular risk. Expert Opin Drug Saf 24(3):241–250. 10.1080/14740338.2025.2462671 - DOI - PubMed
    1. Association AD (2022) Standards of care in diabetes-2023 abridged for primary care providers. Clin Diabetes 41(1):4–31. 10.2337/cd23-as01 - DOI - PMC - PubMed
    1. Perkins BA, Ficociello LH, Silva KH, Finkelstein DM, Warram JH, Krolewski AS (2003) Regression of microalbuminuria in type 1 diabetes. N Engl J Med 348(23):2285–2293. 10.1056/NEJMoa021835 - DOI - PubMed

MeSH terms