The cGAS-STING axis in kidney disease: mechanisms and therapeutic potential

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) axis is a pivotal innate immune signaling pathway that detects cytoplasmic DNA and initiates immune responses. Recent studies have highlighted its critical role in the pathogenesis of various kidney diseases, including acute kidney injury, chronic kidney disease, diabetic kidney disease, lupus nephritis, and kidney cancer. Dysregulated cGAS-STING activation contributes to renal inflammation, fibrosis, and disease progression, making it a promising therapeutic target. This review explores the involvement of the cGAS-STING pathway in multiple renal disorders, emphasizing its dual roles in disease progression and immune regulation. Additionally, we discuss potential therapeutic strategies, including small-molecule inhibitors, agonists, and Traditional Chinese Medicine (TCM) formulations, that may modulate this pathway to attenuate kidney injury. Despite its therapeutic promise, the cGAS-STING axis exhibits complex and context-dependent regulation, with varying effects across different renal diseases. Further research is needed to elucidate its precise molecular mechanisms and optimize targeted interventions for clinical translation.