TGF-β signaling in fibrosis

Growth Factors. 2011 Oct;29(5):196-202. doi: 10.3109/08977194.2011.595714. Epub 2011 Jul 11.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Connective Tissue Growth Factor / metabolism
  • Extracellular Matrix / pathology*
  • Fibroblasts / metabolism
  • Fibrosis / metabolism*
  • Fibrosis / pathology
  • Fibrosis / physiopathology
  • Humans
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Signal Transduction
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta / metabolism*


  • Smad Proteins
  • Transforming Growth Factor beta
  • Connective Tissue Growth Factor
  • Mitogen-Activated Protein Kinases