PKM2 inhibitor suppresses kidney fibrogenesis by disrupting YAP-TEAD-CCN2 transcriptional signaling following ischemia-reperfusion injury.

ABSTRACT: Fibrosis progressively impairs organ function and drives the progression of chronic kidney disease (CKD), for which effective targeted therapies are lacking. Although metabolic reprogramming toward glycolysis promotes fibrosis, the molecular link between metabolic shifts and transcriptional control in CKD and its therapeutic potential has not yet been established. In this study, we demonstrate that pyruvate kinase M2 (PKM2) orchestrates renal fibrosis via nuclear translocation and interaction with the Yes-associated protein (YAP) and beta-catenin (β-catenin) transcriptional networks. Using unilateral ischemia-reperfusion injury mouse models and human renal tubular epithelial cells, we revealed that pharmacological inhibition and genetic knockdown of PKM2 markedly attenuate renal atrophy an

SUBMITTER: Kosakai W 

PROVIDER: S-EPMC12803839 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature