The cGAS-STING pathway in metabolic dysfunction-associated steatotic liver disease: mechanistic insights and therapeutic opportunities
Year: 2026
Type: review
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.
Source: Frontiers in Pharmacology
Authors: Xingxing Yuan, Jing Li, Ying Li, Lei Yang
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221602558