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Cited by 718Liver physiology and pathologyTGF-β signaling in diseasesLiver Disease Diagnosis and Treatment

TGF-β in progression of liver disease

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Dooley, Steven, ten Dijke, Peter·2012·Cell and Tissue Research
DOI 10.1007/s00441-011-1246-yPMC PMC3250614
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Abstract

Transforming growth factor-β (TGF-β) is a central regulator in chronic liver disease contributing to all stages of disease progression from initial liver injury through inflammation and fibrosis to cirrhosis and hepatocellular carcinoma. Liver-damage-induced levels of active TGF-β enhance hepatocyte destruction and mediate hepatic stellate cell and fibroblast activation resulting in a wound-healing response, including myofibroblast generation and extracellular matrix deposition. Being recognised as a major profibrogenic cytokine, the targeting of the TGF-β signalling pathway has been explored with respect to the inhibition of liver disease progression. Whereas interference with TGF-β signalling in various short-term animal models has provided promising results, liver disease progression in humans is a process of decades with different phases in which TGF-β or its targeting might have both beneficial and adverse outcomes. Based on recent literature, we summarise the cell-type-directed double-edged role of TGF-β in various liver disease stages. We emphasise that, in order to achieve therapeutic effects, we need to target TGF-β signalling in the right cell type at the right time.

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  • TGF-β1 is the most potent cytokine that induces HSC activation.

    “Transforming growth factor‐β1 (TGF‐β1) is the most potent cytokine that induces HSC activation”

    From Cellular communication network factor 1‐stimulated liver macrophage efferocytosis drives hepatic stellate cell activation and liver fibrosis (2022) · cites this paper as [6]

    The ‘Hepatic stellate cells’ section says TGF-β makes an important contribution to HSC activation and fibrogenesis. It does not compare its potency with other cytokines or establish that TGF-β1 is the most potent inducer. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Kupffer cells are the major source of TGF-β1 in the liver.

    “for which Kupffer cells (KCs), the resident macrophages in the liver, are the major source.[ 5 , 6 ]”

    From Cellular communication network factor 1‐stimulated liver macrophage efferocytosis drives hepatic stellate cell activation and liver fibrosis (2022) · cites this paper as [6]

    The Carcinogenesis section says that, upon liver damage, non-parenchymal cells produce TGF-β, including macrophages—especially Kupffer cells. It does not establish that Kupffer cells are the major source of TGF-β1 across the liver generally; it also names granulocytes and hepatic stellate cells as producers. No page number is available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Across species, activated HSCs become the dominant source of TGF-β as fibrosis progresses.

    “For example, while macrophages contribute to TGF-β production during early inflammatory stages, across species activated HSCs become the dominant source of TGF-β as fibrosis progresses (133, 134).”

    From Targeting macrophages in liver fibrosis (2026) · cites this paper as [133]

    The Carcinogenesis section (page unavailable) identifies macrophages and HSCs among cells that initiate TGF-β production after liver damage. The Hepatic stellate cells section (page unavailable) describes autocrine TGF-β signalling in activated myofibroblasts, but does not establish that activated HSCs become the dominant source as fibrosis progresses or that this pattern holds across species. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Dooley, S., & ten Dijke, P.
Affiliations
Heidelberg University (DE)
Corresponding author
Dooley, Steven
ORCID
Dooley, Steven
Venue
Cell and Tissue Research
Publisher
Springer Science and Business Media LLC
Published
2011-10-19
Volume
347
Issue
1
Pages
245-256
ISSN
  • 0302-766X (ISSN-L)
  • 1432-0878
DOI
10.1007/s00441-011-1246-y
PMC
PMC3250614
OpenAlex
W2079684286
Cited by
718
References
4
Citations by year
2026: 38 · 2025: 67 · 2024: 47 · 2023: 40 · 2022: 44 · 2021: 74 · 2020: 49 · 2019: 66 · 2018: 60 · 2017: 58 · 2016: 48 · 2015: 36 · 2014: 35 · 2013: 45 · 2012: 9
FWCI
3.70
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Cell and Tissue Research (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Keywords
TGF-beta, chronic liver disease, liver fibrosis, liver cirrhosis, hepatocellular carcinoma, hepatic stellate cells, extracellular matrix deposition, wound healing, liver inflammation, disease progression
MeSH terms
Animals, Chronic Disease, Humans, Liver Diseases, Liver Neoplasms, Signal Transduction, Transforming Growth Factor beta, Disease Progression, Epithelial-Mesenchymal Transition

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