TGF‐β signalling and liver disease
Open accessAbstract
The transforming growth factor‐beta ( TGF ‐β) family signalling pathways play essential roles in the regulation of different cellular processes, including proliferation, differentiation, migration or cell death, which are essential for the homeostasis of tissues and organs. Because of the diverse and pleiotropic TGF ‐β functions, deregulation of its pathways contributes to human disease. In the case of the liver, TGF ‐β signalling participates in all stages of disease progression, from initial liver injury through inflammation and fibrosis, to cirrhosis and cancer. TGF ‐β has cytostatic and apoptotic effects in hepatocytes, promoting liver differentiation during embryogenesis and physiological liver regeneration. However, high levels of TGF ‐β, as a consequence of chronic liver damage, result in activation of stellate cells to myofibroblasts and massive hepatocyte cell death, which contributes to the promotion of liver fibrosis and later cirrhosis. During liver tumorigenesis, TGF ‐β may behave as a suppressor factor at early stages; however, there is strong evidence that overactivation of TGF ‐β signalling might contribute to later tumour progression, once cells escape from its cytostatic effects. For these reasons, targeting the TGF ‐β signalling pathway is being explored to counteract liver disease progression. In this review, we aim to shed light on the state‐of‐the‐art in the signalling pathways induced by TGF ‐β that are involved in different stages of liver physiology and pathology.
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TGF-β is the primary suppressor of liver regeneration, becoming active when the liver reaches the required mass; its function is to halt the cell cycle and stimulate apoptosis in hepatocytes no longer needed for regeneration.
“TGF-β activation: TGF-β is the primary suppressor of LR, becoming active when the liver reaches the required mass. Its function is to halt the cell cycle and stimulate apoptosis in hepatocytes that are no longer needed for regeneration[95].”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [95]
The section “The TGF-b as a guardian of liver homeostasis” describes TGF-β as an important inhibitory signal during liver regeneration and links its signalling to termination of the regenerative response. The Introduction also describes cytostatic and apoptotic effects in hepatocytes as critical to controlling liver mass. The paper does not establish that TGF-β is the primary suppressor, that it becomes active specifically when the required mass is reached, or that apoptosis selectively removes hepatocytes no longer needed for regeneration. (LLM, conf=0.88)
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- Authors
- Fabregat, I., Moreno‐Càceres, J., Sánchez, A., Dooley, S., Dewidar, B., Giannelli, G., ten Dijke, P., & the IT‐LIVER Consortium
- Affiliations
- Institut d'Investigació Biomédica de Bellvitge (ES)
- Department of Biochemistry and Molecular Biology II San Carlos Clinical Hospital Health Research Institute (IdISSC) Madrid Spain
- Heidelberg University (DE)
- Tanta University (EG)
- University of Bari Aldo Moro (IT)
- Department of Molecular and Cell Biology Cancer Genomics Centre Netherlands Leiden The Netherlands
- Corresponding author
- Fabregat, Isabel
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2016-02-22
- Volume
- 283
- Issue
- 12
- Pages
- 2219-2232
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- OpenAlex
- W2471828796
- Cited by
- 600
- References
- 3
- Citations by year
- 2026: 33 · 2025: 42 · 2024: 71 · 2023: 80 · 2022: 79 · 2021: 71 · 2020: 76 · 2019: 52 · 2018: 53 · 2017: 35 · 2016: 8
- FWCI
- 6.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Journal (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Funders
- People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013, n° PITN-GA-2012-316549)
- 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 › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- TGF-beta signaling, liver disease, liver fibrosis, liver cirrhosis, liver regeneration, hepatocyte apoptosis, hepatic stellate cells, myofibroblast activation, hepatocarcinogenesis, liver inflammation, TGF-β inhibitors
- MeSH terms
- Carcinoma, Hepatocellular, Humans, Inflammation, Liver Cirrhosis, Liver Neoplasms, Liver Regeneration, Signal Transduction, Transforming Growth Factor beta, Hepatocytes, Carcinogenesis
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