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Transforming Growth Factor-β Signaling in Alcohol-Associated Liver Disease: A Multicellular Perspective.
Huihui Zou1, Sai Wang1, Chenjun Huang1
1Section Molecular Hepatology, Department of Medicine II, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
The American Journal of Pathology
|October 18, 2025
Summary
Transforming growth factor-β (TGF-β) signaling critically impacts alcohol-associated liver disease (ALD) progression. Understanding TGF-β
Area of Science:
- Hepatology and Immunology
- Molecular Biology and Signaling Pathways
Background:
- Alcohol-associated liver disease (ALD) involves complex cellular and molecular changes.
- Transforming growth factor-β (TGF-β) signaling is implicated in ALD pathogenesis.
- The precise roles of TGF-β in different liver cells during ALD require detailed investigation.
Purpose of the Study:
- To review and synthesize current knowledge on TGF-β signaling in ALD.
- To delineate the context-specific functions of TGF-β in various liver cell types.
- To identify potential therapeutic targets within the TGF-β pathway for ALD.
Main Methods:
- Systematic literature review of PubMed-listed publications (2000-2025) using keywords 'TGF-β', 'alcohol', and 'liver disease'.
- Inclusion of 19 foundational studies predating 2000.
- Analysis of TGF-β's effects on hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells, and immune cells.
Main Results:
- TGF-β promotes hepatocyte injury, metabolic changes, and epithelial-to-mesenchymal transition.
- In hepatic stellate and Kupffer cells, TGF-β is induced by ethanol metabolites and promotes extracellular matrix deposition.
- TGF-β contributes to sinusoidal dysfunction, impaired regeneration, and immune suppression in ALD.
Conclusions:
- TGF-β signaling is a central mediator of liver injury, fibrosis, and progression in ALD.
- Its diverse roles across liver cell types highlight its complex involvement in ALD.
- Targeting cell type-specific TGF-β signaling nodes offers potential for precision therapies in ALD.
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