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WWP2 deletion aggravates acute kidney injury by targeting CDC20/autophagy axis

Ran You1, Yanwei Li2, Yuteng Jiang3

  • 1Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China; Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, China; Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.

Journal of Advanced Research
|June 23, 2024
PubMed
Abstract

Insights

WWP2, an E3 ligase, protects against acute kidney injury (AKI) by regulating CDC20 and autophagy. Activating WWP2 or inhibiting CDC20 may offer new therapeutic strategies for AKI patients.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cellular Biology

Background:

  • Acute kidney injury (AKI) presents significant morbidity and mortality.
  • The molecular underpinnings of AKI are under active investigation.
  • WWP2, an E3 ligase, is known to regulate cell proliferation and differentiation, but its role in AKI is unclear.

Purpose of the Study:

  • To investigate the role of WWP2 in AKI.
  • To elucidate the underlying molecular mechanisms of WWP2 in AKI.

Main Methods:

  • Utilized human AKI renal tissues and mouse models (global/tubule-specific WWP2 knockout).
  • Conducted ubiquitylation omics and quantitative proteomics.
  • Performed experimental validation of identified targets and pathways.

Main Results:

  • WWP2 expression is upregulated in AKI kidneys.
  • WWP2 deficiency exacerbates AKI, while overexpression is protective.
  • WWP2 regulates autophagy via poly-ubiquitylation of CDC20, a negative autophagy regulator.
  • Targeting WWP2/CDC20/autophagy pathway demonstrates therapeutic potential in AKI models.

Conclusions:

  • The WWP2/CDC20/autophagy axis represents a critical intrinsic protective mechanism against AKI.
  • Modulating WWP2 or CDC20 could offer novel therapeutic avenues for AKI.
Keywords:
Acute kidney injuryAutophagyCDC20Tubular epithelial cellsWWP2

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