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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

The cGAS-STING pathway in metabolic dysfunction-associated steatotic liver disease: mechanistic insights and therapeutic opportunities

  • Xingxing Yuan1
  • Jing Li2
  • Ying Li3
  • Lei Yang1
  1. 1Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine
  2. 2Department of Graduate Studies, Academy of Traditional Chinese Medicine
  3. 3Department of Nephrology, Heilongjiang Academy of Traditional Chinese Medicine
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Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic metabolic liver disease worldwide, encompassing a spectrum that includes simple steatosis, metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, and hepatocellular carcinoma (HCC), with immune-metabolic-inflammatory dysregulation at its core pathogenesis. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway serves as the central axis of cytosolic DNA sensing and innate immune activation. Endogenous stimuli, including mitochondrial DNA leakage, DNA damage, and gut microbial DNA translocation, can persistently activate this pathway, which in turn regulates lipid metabolism imbalance, hepatic inflammation amplification, hepatic stellate cell (HSC) activation, and malignant transformation through downstream signaling axes, driving the full spectrum of MASLD pathology. Molecules associated with the cGAS-STING pathway may serve as non-invasive diagnostic biomarkers for MASLD, and natural compounds, traditional Chinese medicine, and nanosystems targeting this pathway have demonstrated promising therapeutic effects. This review systematically summarizes the molecular mechanisms of the cGAS-STING pathway, its regulatory roles in MASLD, and advances in targeted therapy, providing a theoretical foundation for disease mechanism elucidation and the development of diagnostic and therapeutic strategies.

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Cite

BibTeXRIS
BibTeX
@article{yuan2026cgassting,
  title = {{The cGAS-STING pathway in metabolic dysfunction-associated steatotic liver disease: mechanistic insights and therapeutic opportunities}},
  author = {Xingxing Yuan and Jing Li and Ying Li and Lei Yang},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1909062},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1909062/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The cGAS-STING pathway in metabolic dysfunction-associated steatotic liver disease: mechanistic insights and therapeutic opportunities
AU  - Xingxing Yuan
AU  - Jing Li
AU  - Ying Li
AU  - Lei Yang
PY  - 2026
DA  - 2026/10/13
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1909062
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1909062/full
AB  - Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic metabolic liver disease worldwide, encompassing a spectrum that includes simple steatosis, metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, and hepatocellular carcinoma (HCC), with immune-metabolic-inflammatory dysregulation at its core pathogenesis. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway serves as the central axis of cytosolic DNA sensing and innate immune activation. Endogenous stimuli, including mitochondrial DNA leakage, DNA damage, and gut microbial DNA translocation, can persistently activate this pathway, which in turn regulates lipid metabolism imbalance, hepatic inflammation amplification, hepatic stellate cell (HSC) activation, and malignant transformation through downstream signaling axes, driving the full spectrum of MASLD pathology. Molecules associated with the cGAS-STING pathway may serve as non-invasive diagnostic biomarkers for MASLD, and natural compounds, traditional Chinese medicine, and nanosystems targeting this pathway have demonstrated promising therapeutic effects. This review systematically summarizes the molecular mechanisms of the cGAS-STING pathway, its regulatory roles in MASLD, and advances in targeted therapy, providing a theoretical foundation for disease mechanism elucidation and the development of diagnostic and therapeutic strategies.
SN  - 1663-9812
ER  -