Transforming growth factor β latency: a mechanism of cytokine storage and signalling regulation in liver homeostasis and disease
Transforming growth factor-β (TGF-β) is a potent effector in the liver, which is involved in a plethora of processes initiated upon liver injury. TGF-β affects parenchymal, non-parenchymal, and inflammatory cells in a highly context-dependent manner. Its bioavailability is critical for a fast respon...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 2022
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| In: |
JHEP reports
Year: 2022, Volume: 4, Issue: 2, Pages: 1-14 |
| ISSN: | 2589-5559 |
| DOI: | 10.1016/j.jhepr.2021.100397 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1016/j.jhepr.2021.100397 Verlag, kostenfrei, Volltext: https://www.sciencedirect.com/science/article/pii/S2589555921001737 
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| Author Notes: | Yujia Li, Weiguo Fan, Frederik Link, Sai Wang, Steven Dooley |
| Summary: | Transforming growth factor-β (TGF-β) is a potent effector in the liver, which is involved in a plethora of processes initiated upon liver injury. TGF-β affects parenchymal, non-parenchymal, and inflammatory cells in a highly context-dependent manner. Its bioavailability is critical for a fast response to various insults. In the liver - and probably in other organs - this is made possible by the deposition of a large portion of TGF-β in the extracellular matrix as an inactivated precursor form termed latent TGF-β (L-TGF-β). Several matrisomal proteins participate in matrix deposition, latent complex stabilisation, and activation of L-TGF-β. Extracellular matrix protein 1 (ECM1) was recently identified as a critical factor in maintaining the latency of deposited L-TGF-β in the healthy liver. Indeed, its depletion causes spontaneous TGF-β signalling activation with deleterious effects on liver architecture and function. This review article presents the current knowledge on intracellular L-TGF-β complex formation, secretion, matrix deposition, and activation and describes the proteins and processes involved. Further, we emphasise the therapeutic potential of toning down L-TGF-β activation in liver fibrosis and liver cancer. |
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| Item Description: | Online verfügbar: 18. November 2021, Artikelversion: 10. Januar 2022 Im Titel ist beta als griechischer Buchstabe geschrieben Gesehen am 07.05.2024 |
| Physical Description: | Online Resource |
| ISSN: | 2589-5559 |
| DOI: | 10.1016/j.jhepr.2021.100397 |