OTUD7B attenuates renal fibrosis by regulating PRDX1 protein stability

Yufeng Xiong1, Xiaojie Zhao2, Xuke Qin3

  • 1Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China; Institute of Urologic Disease, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.

PubMed
Abstract

Insights

The deubiquitinating enzyme OTUD7B protects against renal fibrosis by stabilizing PRDX1. Targeting the OTUD7B-SMURF1-PRDX1 pathway offers a new therapeutic strategy for kidney fibrosis.

Area of Science:

  • Nephrology
  • Epigenetics
  • Molecular Biology

Background:

  • Renal fibrosis is a common endpoint for chronic kidney disease (CKD) and end-stage renal disease (ESRD).
  • Epigenetic modifications are increasingly recognized for their role in renal fibrosis development.
  • Understanding the molecular mechanisms underlying renal fibrosis is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of the deubiquitinating enzyme OTUD7B in renal fibrosis.
  • To elucidate the underlying molecular mechanisms by which OTUD7B influences renal fibrosis.
  • To identify potential therapeutic targets for renal fibrosis based on OTUD7B's function.

Main Methods:

  • Transcriptome sequencing to identify key deubiquitinating enzymes in fibrosis.
  • Validation of OTUD7B expression in cellular, animal, and human kidney samples.
  • Knockdown and overexpression studies to determine OTUD7B's functional role in renal fibrosis.
  • Co-immunoprecipitation and mass spectrometry (IP-MS) to identify OTUD7B interacting partners.
  • Ubiquitination assays to analyze PRDX1 modification and stability.

Main Results:

  • OTUD7B expression was reduced in renal fibrosis and validated across multiple models.
  • Overexpression of OTUD7B attenuated renal fibrosis, while knockdown exacerbated it.
  • OTUD7B was found to interact with PRDX1 and reduce its ubiquitination mediated by SMURF1.
  • This mechanism led to increased PRDX1 protein stability and expression, ultimately mitigating renal fibrosis.

Conclusions:

  • OTUD7B plays a protective role against renal fibrosis.
  • The OTUD7B-SMURF1-PRDX1 axis is a key pathway regulating renal fibrosis.
  • Targeting this axis presents a promising therapeutic strategy for treating renal fibrosis.

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