Regulation of PKM2 expression and function by GLIS3 during metabolic reprogramming in polycystic kidneys - PubMed
5 hours ago
- #PKM2
- #Polycystic Kidney Disease
- #Metabolic Reprogramming
- GLIS3 deficiency in humans and mice leads to polycystic kidney disease (PKD).
- GLIS3 knockout (KO) kidneys show increased reliance on aerobic glycolysis due to metabolic reprogramming.
- Transcriptomic analysis revealed upregulation of glycolytic genes and downregulation of gluconeogenic genes in Glis3-KO kidneys.
- GLIS3 regulates glycolytic gene expression in coordination with transcription factor HNF-1B.
- PKM2, a glycolytic enzyme, is upregulated in Glis3-KO kidneys and promotes aerobic glycolysis.
- Phosphorylation of PKM2 at Y105 and S37 enhances dimer formation, nuclear localization, and aerobic glycolysis in Glis3-KO kidneys.
- Knockdown or pharmacological inhibition of PKM2 reduces spheroid growth, glycolytic activity, and cyst formation in GLIS3-deficient models.
- GLIS3 is identified as a novel regulator of glycolysis and PKM2 function, contributing to cystogenesis in PKD.