Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-β as major players and therapeutic targets
Open accessAbstract
Hepatic fibrosis is a scarring process that is associated with an increased and altered deposition of extracellular matrix in liver. At the cellular and molecular level, this progressive process is mainly characterized by cellular activation of hepatic stellate cells and aberrant activity of transforming growth factor‐β1 and its downstream cellular mediators. Although the cellular responses to this cytokine are complex, the signalling pathways of this pivotal cytokine during the fibrogenic response and its connection to other signal cascades are now understood in some detail. Based on the current advances in understanding the pleiotropic reactions during fibrogenesis, various inhibitors of transforming growth factor‐β were developed and are now being investigated as potential drug candidates in experimental models of hepatic injury. Although it is too early to favour one of these antagonists for the treatment of hepatic fibrogenesis in human, the experimental results obtained yet provide stimulatory impulses for the development of an effective treatment of choice in the not too distant future. The present review summarises the actual knowledge on the pathogenesis of hepatic fibrogenesis, the role of transforming growth factor‐β and its signalling pathways in promoting the fibrogenic response, and the therapeutic modalities that are presently in the spotlight of many investigations and are already on the way to take the plunge into clinical studies.
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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 [134]
The available overview passage links hepatic stellate-cell activation and TGF-β activity to progressive liver fibrosis, but does not identify which cells produce TGF-β. Searches for macrophage production, a shift to stellate cells as the dominant source, and cross-species evidence found no passage addressing those claims. (LLM, conf=0.72)
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Targeting macrophages in liver fibrosis
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- Authors
- Gressner, A. M., & Weiskirchen, R.
- Affiliations
- Universitätsklinikum Aachen (DE)
- Corresponding author
- Gressner, A. M.
- ORCID
- Weiskirchen, R.
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2006-01
- Volume
- 10
- Issue
- 1
- Pages
- 76-99
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC3933103
- OpenAlex
- W1963780536
- Cited by
- 718
- References
- 4
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 10 · 2023: 21 · 2022: 24 · 2021: 30 · 2020: 29 · 2019: 36 · 2018: 48 · 2017: 53 · 2016: 54 · 2015: 42 · 2014: 44 · 2013: 48 · 2012: 39
- FWCI
- 5.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (TP A9)
- Bundesministerium für Bildung und Forschung
- 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
- liver fibrosis, hepatic stellate cells, TGF-β1, TGF-beta signaling, extracellular matrix deposition, fibrogenesis, TGF-beta antagonists, antifibrotic therapy, liver injury
- MeSH terms
- Cell Differentiation, Collagen, Extracellular Matrix, Gene Expression Regulation, Glycosaminoglycans, Humans, Liver, Liver Cirrhosis, Models, Biological, Signal Transduction, Transforming Growth Factor beta, Extracellular Matrix Proteins, Receptors, Transforming Growth Factor beta, Protein Structure, Quaternary, Smad Proteins
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