cGAS-STING signaling pathway in MASLD and liver fibrosis.

Abstract

In metabolic dysfunction-associated steatotic liver disease (MASLD), lipid accumulation and inflammatory stimulation lead to the release of damage-associated molecular patterns, thereby inducing the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. The cGAS-STING signaling pathway in the liver is primarily activated in Kupffer cells/macrophages, hepatic stellate cells, hepatocytes and liver sinusoidal endothelial cells. Emerging evidence also reveals that the cGAS-STING signaling pathway contributes to liver cell fate changes in MASLD. Herein, this review summarizes the role of the cGAS-STING signaling pathway in liver cells and its effect on cell fate in the context of MASLD and liver fibrosis. Therapeutic agents targeting the cGAS-STING signaling pathway may shed light on the clinical treatment of MASLD and liver fibrosis.