Role of cGAS-STING pathway in fibrotic disease

Abstract

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway serves as a central sensor of cytosolic DNA, orchestrating innate immune responses and maintaining tissue homeostasis. However, dysregulated activation of this signaling cascade has been implicated in chronic inflammation, aberrant tissue remodeling, and the development of fibrosis across multiple organs. Fibrosis, a pathological process characterized by excessive extracellular matrix deposition, underlies progressive dysfunction in the lungs, liver, kidneys, heart, and skin. Recent studies have revealed that abnormal cGAS-STING signaling influences both immune and stromal cell responses, thereby linking DNA sensing to fibrotic progression. In this review, we summarize the current understanding of cGAS-STING in fibrotic diseases, discuss its cellular and molecular mechanisms, and highlight therapeutic strategies targeting this pathway. These insights provide a comprehensive perspective on cGAS-STING as a potential intervention point for diverse fibrotic disorders.

Keywords: CGAS-STING; Fibroblast; Fibrotic disease; Immune system; dsDNA.