Glycolysis drives STING signaling to promote M1-macrophage polarization and aggravate liver fibrosis.

ABSTRACT: Glycolysis activation plays a critical role in sustaining the proinflammatory phenotype of macrophages, which is key to initiating and advancing liver fibrosis. However, the underlying mechanisms that trigger glycolytic activation and their contribution to inflammation remain poorly understood. In this study, we showed that inhibiting glycolysis markedly suppresses macrophage M1 polarization and alleviates liver inflammation and fibrosis, whereas enhancing glycolysis in hepatic macrophages produces the opposite effect. Additionally, our results demonstrated that glycolytic flux is necessary for activation of the STING/TBK1/IRF3 pathway. Moreover, STING activation was found to reciprocally stimulate glycolysis in macrophages. Mechanistically, we found that ATP generated through glycolysis p

SUBMITTER: Chen P 

PROVIDER: S-EPMC12594590 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature