TY - JOUR
T1 - Transforming growth factor–β in tissue fibrosis
AU - Frangogiannis, Nikolaos G.
N1 - Funding Information:
N.G. Frangogiannis’s laboratory is supported by National Institutes of Health grants R01 HL76246 and R01 HL85440 and US Department of Defense grants PR151134, PR151029, and PR181464.
Publisher Copyright:
© 2020 Frangogiannis. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
PY - 2020/3/2
Y1 - 2020/3/2
N2 - 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.
AB - 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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U2 - 10.1084/jem_20190103
DO - 10.1084/jem_20190103
M3 - Review article
C2 - 32997468
AN - SCOPUS:85088408972
SN - 0022-1007
VL - 217
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
M1 - e20190103
ER -