Transforming growth factor-β in tissue fibrosis
TGF-β is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation of bioactive TGF-β from latent stores requires the cooperation of proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets of TGF-...
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| Published in: | The Journal of experimental medicine Vol. 217; no. 3; p. e20190103 |
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| Main Author: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
02.03.2020
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| ISSN: | 1540-9538, 1540-9538 |
| Online Access: | Get more information |
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| Summary: | TGF-β is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation of bioactive TGF-β from latent stores requires the cooperation of proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets of TGF-β, some fibrogenic actions may reflect activation of other cell types, including macrophages, epithelial cells, and vascular cells. TGF-β-driven fibrosis is mediated through Smad-dependent or non-Smad pathways and is modulated by coreceptors and by interacting networks. This review discusses the role of TGF-β in fibrosis, highlighting mechanisms of TGF-β activation and signaling, the cellular targets of TGF-β actions, and the challenges of therapeutic translation.TGF-β is extensively implicated in the pathogenesis of fibrosis. In fibrotic lesions, spatially restricted generation of bioactive TGF-β from latent stores requires the cooperation of proteases, integrins, and specialized extracellular matrix molecules. Although fibroblasts are major targets of TGF-β, some fibrogenic actions may reflect activation of other cell types, including macrophages, epithelial cells, and vascular cells. TGF-β-driven fibrosis is mediated through Smad-dependent or non-Smad pathways and is modulated by coreceptors and by interacting networks. This review discusses the role of TGF-β in fibrosis, highlighting mechanisms of TGF-β activation and signaling, the cellular targets of TGF-β actions, and the challenges of therapeutic translation. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 |
| ISSN: | 1540-9538 1540-9538 |
| DOI: | 10.1084/jem.20190103 |