title: TGF-β signaling in fibrosis.
abstract: Transforming growth factor β (TGF-β) is a central mediator of fibrogenesis. TGF-β is upregulated and activated in fibrotic diseases and modulates fibroblast phenotype and function, inducing myofibroblast transdifferentiation while promoting matrix preservation. Studies in a wide range of experimental models have demonstrated the involvement of the canonical activin receptor-like kinase 5/Smad3 pathway in fibrosis. Smad-independent pathways may regulate Smad activation and, under certain conditions, may directly transduce fibrogenic signals. The profibrotic actions of TGF-β are mediated, at least in part, through induction of its downstream effector, connective tissue growth factor. In light of its essential role in the pathogenesis of fibrosis, TGF-β has emerged as an attractive therapeutic target. However, the pleiotropic and multifunctional effects of TGF-β and its role in tissue homeostasis, immunity and cell proliferation raise concerns regarding potential side effects that may be caused by TGF-β blockade. This minireview summarizes the role of TGF-β signaling pathways in the fibrotic response.
authors: Division of Cardiology, Albert Einstein College of Medicine, Bronx, NY 14016, USA. nikolaos.frangogiannis@einstein.yu.edu
authors: Anna
authors: A
authors: Biernacka
authors: Marcin
authors: M
authors: Dobaczewski
authors: Nikolaos G
authors: NG
authors: Frangogiannis
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D005109:Extracellular Matrix / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D020928:Mitogen-Activated Protein Kinases