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DUSP26 protects against acute kidney injury by dephosphorylating p53 at serine 312

Ying Fu1,2,3, Yu Xiang1, Yun Han1

  • 1Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, Institute of Nephrology, The Second Xiangya Hospital at Central South University, Changsha, China.

Nature Communications
|February 26, 2026
PubMed

Insights

Dual-specificity phosphatase 26 (DUSP26) protects against acute kidney injury (AKI) by regulating p53. Reduced DUSP26 expression exacerbates kidney tubule damage, while its restoration offers protection, revealing a potential therapeutic target.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Acute kidney injury (AKI) is a major cause of patient mortality.
  • The molecular mechanisms underlying kidney tubule damage in AKI are not fully elucidated.
  • Identifying novel regulators of AKI is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of dual-specificity phosphatase 26 (DUSP26) in kidney tubule injury during AKI.
  • To elucidate the molecular mechanisms by which DUSP26 influences AKI.
  • To evaluate the therapeutic potential of targeting the DUSP26-p53 pathway in AKI.

Main Methods:

  • Analysis of DUSP26 expression in human kidney biopsies and murine AKI models.
  • Investigation of DUSP26 promoter methylation in kidney tubular cells.
  • Assessment of DUSP26 function using gene knockout and knock-in models.
  • Biochemical assays to determine DUSP26 interaction with p53.
  • Pharmacological manipulation of DUSP26 activity in AKI and liver ischemia-reperfusion injury models.

Main Results:

  • DUSP26 expression is significantly reduced in kidney biopsies from AKI patients and in murine AKI models.
  • Reduced DUSP26 expression in AKI is associated with hypermethylation of its gene promoter.
  • Loss of DUSP26 exacerbates kidney tubule injury, whereas DUSP26 expression confers protection.
  • DUSP26 directly dephosphorylates p53 at serine 312, reducing p53-mediated apoptosis.
  • Pharmacological inhibition of DUSP26 worsens AKI and liver injury, while DUSP26 overexpression is protective.

Conclusions:

  • DUSP26 is a critical regulator of kidney tubule injury in AKI.
  • The DUSP26-p53 signaling axis plays a key role in protecting against AKI.
  • DUSP26 dephosphorylates p53 to dampen pro-apoptotic signaling.
  • Targeting the DUSP26-p53 pathway represents a promising therapeutic strategy for AKI.

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