Transforming growth factor–β in tissue fibrosis
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 20, 2020
- Source ID
- 10.1084/jem.20190103
Entities
People
- Nikolaos G Frangogiannis
Organizations
- Albert Einstein College of Medicine
- National Institutes of Health
- United States Department of Defense