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FXR acts as a therapeutic target for ulcerative colitis via suppressing ferroptosis

Chenye Zhao1, Xiaopeng Li1, Mingchao Mu1

  • 1Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.

Molecular Medicine (Cambridge, Mass.)
|July 18, 2025
PubMed
Abstract

Insights

Farnesoid X receptor (FXR) antagonizes ferroptosis, offering a potential therapeutic strategy for ulcerative colitis (UC). This study demonstrates FXR

Area of Science:

  • Gastroenterology
  • Cell Biology
  • Molecular Medicine

Background:

  • Ferroptosis involvement in ulcerative colitis (UC) is recognized.
  • Farnesoid X receptor (FXR) mechanisms inhibiting ferroptosis in other diseases are known.
  • FXR's role in UC ferroptosis remains uninvestigated.

Purpose of the Study:

  • To investigate the role of FXR in modulating ferroptosis in ulcerative colitis.
  • To explore FXR's therapeutic potential in UC by targeting ferroptosis.

Main Methods:

  • Evaluated FXR expression in colitis models (GEO database, patient samples, DSS-induced colitis mice).
  • Administered intestine-restricted FXR agonist fexaramine (Fex) to colitis mice.
  • Utilized in vitro Caco-2 cells challenged with RSL3 to study FXR's effect on ferroptosis in intestinal epithelial cells.

Main Results:

  • Fex treatment alleviated UC symptoms and reduced ferroptosis in mice.
  • Fex protected Caco-2 cells from RSL3-induced ferroptosis in vitro.
  • FXR upregulates SLC7A11 transcription for GSH synthesis and increases GPX4 stability via OTUB1.

Conclusions:

  • FXR exerts therapeutic effects in colitis by inhibiting ferroptosis.
  • FXR antagonizes ferroptosis through SLC7A11 transactivation and GPX4 stabilization.
  • FXR represents a potential therapeutic target for colitis treatment by modulating ferroptosis.
Keywords:
ColitisFXRFerroptosisGPX4OTUB1SLC7A11

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