Delactylase effects of SIRT3 on a positive feedback loop involving the RUNX1-glycolysis-histone lactylation in diabetic kidney disease.

ABSTRACT: Background: Persistently elevated glycolysis is increasingly recognized as a driving force in diabetic kidney disease (DKD). As a product of glycolysis, lactate can induce histone lactylation, an emerging epigenetic mechanism associated with post-transcriptional modification. However, the molecular mechanism and clinical impact of histone lactylation in DKD remain largely understood. Methods and Results: Spatial transcriptomics analysis revealed upregulation of glycolytic genes in tubular epithelial cells (TECs), thus leading to elevated levels of renal lactate accumulation. PKM2 deficiency lowered the lactate production during the fibrotic process and decreased histone lactylation. Mechanistically, ChIP-seq & RNA-seq results showed lactate promoted histone H4 lysine 12 lacty

SUBMITTER: Shen S 

PROVIDER: S-EPMC12905586 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature