IRF7 links HK1-dependent histone lactylation to fibroblast activation and cardiac fibrosis

ABSTRACT: In response to various stimuli, quiescent resident cardiac fibroblasts undergo metabolic, morphological, and functional alterations, transitioning into myofibroblasts that mediate cardiac fibrosis. In the present study, we investigated the role of interferon regulatory factor 7 (IRF7) in fibroblast activation and cardiac fibrosis. Knockdown of IRF7 in quiescent cardiac fibroblasts potentiated myofibroblast transition, whereas over-expression of IRF7 suppressed it. Furthermore, targeted deletion of IRF7 in fibroblasts or myofibroblasts exacerbated cardiac fibrosis and impaired heart function in animal models of heart failure. Integrated transcriptomic analysis revealed hexokinase 1 (HK1) as an IRF7 downstream target. Consistently, genetic deletion or pharmacological inhibition of HK1 protec

SUBMITTER: Ming Kong 

PROVIDER: S-SCDT-10_1038-S44321-026-00444-2 | biostudies-other |

REPOSITORIES: biostudies-other