Evidence map›Paper›PMID 40681992›Full record

ArticleMolecular medicine (Cambridge, Mass.)2025

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

Chenye Zhao, Xiaopeng Li, Mingchao Mu, Liyong Quan, Hang Yuan, Jianbao Zheng, Wei Zhao, Xuejun Sun, Junhui Yu

Abstract read
In one paragraph

Article in Molecular medicine (Cambridge, Mass.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Chenye ZhaoDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
Xiaopeng LiDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
Mingchao MuDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
Liyong QuanDepartment of Orthopedic, Xi'an Chest Hospital, Xi'an, Shaanxi Province, 710100, China.
Hang YuanDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
Jianbao ZhengDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
Wei ZhaoDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China.
Xuejun SunDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China. sunxy@mail.xjtu.edu.cn.
Junhui YuDepartment of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, 710061, China. yujunhui@mail.xjtu.edu.cn.

Funding

National Natural Science Foundation of China 82002547
6 · The paper itself

Abstract

backgroundThe involvement of ferroptosis in ulcerative colitis (UC) is increasingly acknowledged. Several investigations have revealed the various mechanisms by which the farnesoid X receptor (FXR) inhibits ferroptosis in certain diseases; however, its potential modulation of ferroptosis in UC remains unexplored.

methodsThe characteristics of FXR expression in colitis were evaluated in the GEO database, patient specimens, and mice with DSS-induced colitis. The role of FXR in ferroptosis was investigated by treating colitis mice with the intestine-restricted FXR agonist fexaramine (Fex) intragastrically. In vitro, Caco-2 cells challenged with RSL3 were used to study the role of FXR in modulating ferroptosis in intestinal epithelial cells (IECs).

resultsFex significantly alleviated symptoms and impeded ferroptosis in mice with DSS-induced colitis. In vitro, Fex rescued Caco-2 cells from RSL3-induced ferroptosis. Mechanistically, FXR was capable of binding to the promoter region of SLC7A11 and upregulated the transcription of SLC7A11, which is beneficial for the synthesis of GSH. Knockdown of SLC7A11 partially abrogated the therapeutic effects of Fex, albeit incompletely. Further investigations revealed that FXR can also increase the protein stability of GPX4 by upregulating the deubiquitinase OTUB1.

conclusionThis study highlights that FXR exerts therapeutic effects against colitis by antagonizing ferroptosis via transactivation of SLC7A11 and increasing GPX4 stability. These results suggest that FXR may be a therapeutic target for treating colitis by antagonizing ferroptosis.

Indexed as

Colitis, UlcerativeFerroptosisReceptors, Cytoplasmic and NuclearAmino Acid Transport System y+AnimalsCaco-2 CellsDisease Models, AnimalHumansMaleMiceReceptor, Farnesoid X-ActivatedAmino Acid Transport System y+Receptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearSLC7A11 protein, humanColitisFerroptosisFXRGPX4OTUB1SLC7A11

Identifiers

PMID40681992
PMCPMC12273381

What Socratic holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.