Wnt/β-catenin/ATF3 signaling promotes the progression from acute kidney injury to chronic kidney disease by regulating mitophagy in mice

Oct 21, 2025Biochemical pharmacology

Wnt/β-catenin/ATF3 signaling may promote kidney damage from sudden injury to long-term disease by controlling removal of damaged mitochondria in mice

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Abstract

Patients with kidney disease exhibited markedly elevated ATF3 levels compared with healthy controls.

  • Sustained activation of Wnt/β-catenin signaling may promote the progression from acute kidney injury (AKI) to chronic kidney disease (CKD).
  • Wnt1 overexpression in cell models disrupted mitochondrial structure and shifted dynamics toward fission while impairing mitophagy.
  • In vivo models showed similar mitochondrial changes, with KP6 treatment partially rescuing these defects.
  • ATF3 levels were found to correlate positively with serum creatinine, blood urea nitrogen, renal fibrosis, and glomerulosclerosis, and negatively with estimated glomerular filtration rate (eGFR).
  • Exogenous ATF3 impaired mitochondrial function, while silencing ATF3 preserved it, suggesting its role in mitochondrial dynamics.
  • ATF3 may serve as a potential biomarker for the progression from AKI to CKD.

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