Targeting <i>Ogt</i> in ADPKD mitigates metabolic reprogramming and renal cystogenesis, extending survival.

ABSTRACT: Aberrant cell metabolism drives autosomal dominant polycystic kidney disease (ADPKD). O-GlcNAcylation, a metabolically regulated post-translational modification, is elevated in ADPKD kidneys. Using rapidly and slowly progressive ADPKD mouse models, we demonstrate that deleting O-GlcNAc transferase (Ogt) reduces renal cystogenesis and extends survival in a rapidly progressive model from postnatal day 21 to over a year. Pharmacological OGT inhibition similarly reduced cyst formation of patient-derived renal epithelial cells in vitro. In Pkd1 conditional knockout kidneys, Ogt deletion maintained phosphorylated AMPK and mitochondrial respiratory chain complex levels, preserving cellular energy sensing and production. Further, metabolomic analysis revealed normalizat

SUBMITTER: Kavanaugh MA 

PROVIDER: S-EPMC12724162 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature