Evidence mapPaperPMID 41284206Full record

ArticleMolecular biomedicine2025

Epithelial membrane protein 1 drives hepatic stellate cell activation via the TLN1/FAK cascade in MASLD donor liver transplantation.

Tongxi Li, Ran Liu, Huan Cao, Shenghe Deng, Gengqiao Wang, Xueling Wang, Peng Zhao, Xuan Li, Jingjin Zhu, Shuyu Shao and 5 more

Abstract read
In one paragraph

Article in Molecular biomedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

2 citing papers in PubMed.

  1. Review
  2. Review
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

15 authors.

Tongxi Li *Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Ran Liu *Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Huan Cao *Center for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Shenghe DengCenter for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Gengqiao WangDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Xueling WangDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Peng ZhaoDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Xuan LiDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Jingjin ZhuDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Shuyu ShaoDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Hao ChenDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Lei LiuDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Chen ZhangCenter for Liver Transplantation, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Chuanzheng YinDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. dryincz@hust.edu.cn.
Zifang SongDepartment of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. zsong@hust.edu.cn.

Funding

National Natural Science Foundation of China 81974040National Natural Science Foundation of China 82270412National Natural Science Foundation of China 8250036595Postdoctor Project of Hubei Province 2024HBBHCXA040
6 · The paper itself

Abstract

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has significantly increased, prompting the increased use of steatotic donor livers in transplantation, contributing to a higher incidence and severity of ischemia-reperfusion injury (IRI), necessitating the development of targeted interventions for MASLD-related liver transplantation (MASLD-IRI). Here, we identified epithelial membrane protein 1 (EMP1) as a potential diagnostic and therapeutic target in MASLD-IRI using multi-omics analysis and mechanistic investigations in rodent models and cells, further validating our findings in human samples. Phenotypic observations revealed significant activation of hepatic stellate cells (HSCs) under MASLD-IRI conditions, leading to increased inflammatory liver injury, which correlated with significant upregulation of EMP1 in HSC. Mechanistically, EMP1 upregulation inhibited SMAD-specific E3 ubiquitin-protein ligase 1 (SMURF1)-mediated ubiquitination and degradation of talin1 (TLN1) by competing with SMURF1 for the TLN1 binding site. The subsequent accumulation of TLN1 further promoted phosphorylation of focal adhesion kinase (FAK), establishing a pro-inflammatory signaling axis-EMP1/TLN1/FAK-that amplified HSC activation and aggravated liver injury. Silencing EMP1 suppressed the TLN1/FAK post-translational modification cascade, thereby attenuating HSC activation and downstream inflammation. These findings highlight the potential of EMP1 as a biomarker to monitor the prognosis of MASLD transplantation, as well as a therapeutic target to improve prognosis.

Indexed as

Fatty LiverFocal Adhesion Kinase 1Hepatic Stellate CellsLiver TransplantationTalinAnimalsHumansMaleMiceRatsReperfusion InjurySignal TransductionTissue DonorsUbiquitinationUbiquitin-Protein LigasesFocal Adhesion Kinase 1TalinTLN1 protein, humanUbiquitin-Protein LigasesEpithelial membrane protein 1Hepatic Stellate CellIschemia/reperfusion injuryLiver TransplantationMetabolic dysfunction-associated steatotic liver disease

Identifiers

PMID41284206
PMCPMC12644329

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

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.