Evidence map›Paper›PMID 42518287›Full record

ArticleThe Journal of clinical investigation2026

TGF-β serves as a critical signaling determinant of liver progenitor cell activation and function.

Chenhao Tong, Tao Lin, Han Wang, Luyao Jiang, Xiaodong Yuan, Wenwu Luo, Minghan Zhou, Carolina De La Torre, Hui Liu, Chen Shao and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. [The logic of survival in patients with acute liver failure].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025
    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

20 authors.

Chenhao TongDepartment of Medicine II, Section Molecular Hepatology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Tao LinDepartment of Medicine II, Section Molecular Hepatology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Han WangDepartment of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA.
Luyao JiangLiver Disease Research Laboratory, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
Xiaodong YuanDepartment of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Wenwu LuoDepartment of Pathology, The First Affiliated Hospital of Anhui Medical University, Anhui, China.
Minghan ZhouDepartment of Medicine II, Section Molecular Hepatology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Carolina De La TorreNGS Core Facility, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Hui LiuDepartment of Pathology, Beijing You'an Hospital affiliated with Capital Medical University, Beijing, China.
Chen ShaoDepartment of Pathology, Beijing You'an Hospital affiliated with Capital Medical University, Beijing, China.
Seddik HammadDepartment of Medicine II, Section Molecular Hepatology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Hui GaoDepartment of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Jiarong XieDepartment of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Lei XuDepartment of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, China.
Roman LiebeDepartment of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Essen, Germany.
Zuguang GuInstitute of Cell and Gene Technology, Shenzhen University of Advanced Technology, Shenzhen, China.
Matthias P EbertDepartment of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Huiguo DingDepartment of Gastroenterology and Hepatology, Beijing You'an Hospital affiliated with Capital Medical University, Beijing, China.
Steven DooleyDepartment of Medicine II, Section Molecular Hepatology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Hong-Lei WengDepartment of Medicine II, Section Molecular Hepatology, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

When massive hepatic necrosis-associated (MHN-associated) acute liver failure (ALF) occurs following severe damage, liver progenitor cells (LPCs) exit quiescence and enter differentiation programs during which they acquire hepatocyte-like functions. How LPCs maintain quiescence under physiological conditions and orchestrate activation following MHN remains largely unknown. We elucidate an essential role of TGF-β in regulating LPC quiescence and activation. Spatial transcriptomics and single-cell sequencing revealed that LPCs receive multiple signals, particularly TGF-β, HGF, and EGF, from surrounding hepatic stellate cells and macrophages in patients and zebrafish with MHN-induced ALF. Physiologically, TGF-β inhibits LPC proliferation by blocking G1-to-S phase transition, an effect reversed by Smad7 overexpression in a murine injury model. We observed extensive LPC proliferation in patients with ALF despite strong TGF-β/phosphorylated SMAD signaling. Immunostaining revealed concurrent activation of HGF/MET, EGF/EGFR, and downstream STAT3/ERK pathways in LPCs. In vitro, HGF or EGF overcame TGF-β-mediated growth arrest and promoted LPC proliferation. Beyond acting as a mitogen, HGF additionally induced hepatocyte gene programs (e.g., Hnf4a, Hnf1a) in LPCs. Strikingly, TGF-β signaling was required for HGF-dependent hepatocyte gene induction, indicating a dual role in restraining LPC proliferation and promoting functional maturation. These findings position TGF-β as a context-dependent determinant of LPC activation and lineage specification during ALF.

Indexed as

LiverLiver Failure, AcuteSignal TransductionStem CellsTransforming Growth Factor betaAnimalsCell ProliferationEpidermal Growth FactorHepatocyte Growth FactorHepatocytesHumansMiceSmad7 ProteinZebrafishEpidermal Growth FactorHepatocyte Growth FactorSmad7 ProteinSmad7 protein, mouseTransforming Growth Factor betaAdult stem cellsCell biologyCell cycleHepatology

Identifiers

PMID42518287
PMCPMC13574154

What Socratic holds

Textmetadata
Read underepoch 390

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.