TGF-β signaling in fibrosis

Anna Biernacka, Marcin Dobaczewski, Nikolaos G. Frangogiannis

Research output: Contribution to journalArticle

412 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)196-202
Number of pages7
JournalGrowth Factors
Volume29
Issue number5
DOIs
StatePublished - Oct 2011

Fingerprint

Transforming Growth Factors
Fibrosis
Tissue homeostasis
Connective Tissue Growth Factor
Myofibroblasts
Cell proliferation
Fibroblasts
Immunity
Homeostasis
Theoretical Models
Chemical activation
Cell Proliferation
Phenotype

Keywords

  • Collagen
  • Fibrosis
  • MAPK
  • Smad
  • TGF-β

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

TGF-β signaling in fibrosis. / Biernacka, Anna; Dobaczewski, Marcin; Frangogiannis, Nikolaos G.

In: Growth Factors, Vol. 29, No. 5, 10.2011, p. 196-202.

Research output: Contribution to journalArticle

Biernacka, Anna ; Dobaczewski, Marcin ; Frangogiannis, Nikolaos G. / TGF-β signaling in fibrosis. In: Growth Factors. 2011 ; Vol. 29, No. 5. pp. 196-202.
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