The Role of cGAS – STING Pathway in Chronic Liver Diseases: Mechanisms and Therapeutic Perspectives

The signaling pathway of cyclic GMP-AMP synthase (cGAS) and the stimulator of interferon genes (STING), responsible for detecting intracellular DNA and triggering the innate immune response, has emerged as a pivotal contributor in the realm of liver diseases, in particular, concerning their pathogenesis and specific treatment in recent years. Notably, during the progression of chronic liver diseases, cGAS recognizes aberrant DNA and mediates the generation of 2' 3' cyclic GMP-AMP (cGAMP). cGAMP, serving as a second messenger, binds to STING, eliciting its conformational change and subsequently activating downstream signaling molecules including IRF3 and TBK1, boosting cascaded serial reactions responsible for the production of type I interferons (IFN) and the release of various pro-inflammatory cytokines. Given the substantial involvement pertinent to the cGAS-STING pathway in liver diseases, it has become an important target in hopes of addressing novel therapeutic strategies. By targeted inhibition of STING activity, blockade of its downstream signal transduction, or modulation of the expression of pathway-related molecules, there is potential to provide effective treatments in the manner of reducing liver inflammation, repressing fibrogenic progression, and protecting hepatocytes from devastating damage.