Evidence map›Paper›PMID 42003922›Full record

ArticleInternational journal of biological sciences2026

Macrophage NEDD4L restrains liver fibrosis by preventing scar-associated macrophage expansion via ubiquitination of phospho-SMAD3.

Yanghuan He, Shujun Ge, Shijia Ling, Siting Yang, Feiran Yang, Xinyi Liu, Siyue Dong, Yingfen Chen, Ziling Zhang, Yue Zhou and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of biological sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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.

Yanghuan HeDepartment of Gastroenterology, Huadong Hospital, Fudan University, Shanghai, China.
Shujun GeSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Shijia LingSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Siting YangSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Feiran YangSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Xinyi LiuSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Siyue DongSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Yingfen ChenState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China.
Ziling ZhangSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Yue ZhouState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China.
Seonghwan HwangCollege of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, Republic of Korea.
Seung-Jin KimDepartment of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Republic of Korea.
Peng WangDepartment of Hepatobiliary Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
Yong HeSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China.
Yuanwen ChenDepartment of Gastroenterology, Huadong Hospital, Fudan University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Liver fibrosis is characterized by excessive extracellular matrix deposition and hepatic stellate cell (HSC) activation, driven by chronic liver injury and inflammation. Macrophages play dual roles in fibrogenesis; the dynamic balance between pro-fibrotic and anti-fibrotic subsets is critical in determining the progression or regression of the disease. NEDD4L, an E3 ubiquitin ligase, is well-known to be involved in cell biological processes by promoting protein degradation, yet its role in macrophages and liver fibrosis remains poorly understood. Methods: Myeloid cell-specific Results: Single-cell RNA sequencing and transcriptomic analyses revealed significant upregulation of Conclusions: NEDD4L serves as a critical negative regulator of liver fibrosis by restraining profibrotic SAM expansion through ubiquitination and degradation of p-SMAD3 in macrophages. These findings highlight that targeting the ubiquitin-proteasome system as a potential therapeutic strategy for the treatment of fibrotic disease.

Indexed as

Liver CirrhosisMacrophagesNedd4 Ubiquitin Protein LigasesSmad3 ProteinAnimalsHumansMaleMiceMice, KnockoutUbiquitinationNedd4l protein, mouseNedd4 Ubiquitin Protein LigasesSmad3 ProteinSmad3 protein, mouseliver fibrogenesismacrophage differentiationp-SMAD3.ubiquitination

Identifiers

PMID42003922
PMCPMC13085682

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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 OpenQuestion graph.