World J Gastroenterol 13(22): 3056-3062

Transforming growth factor-β and fibrosis

Franck Verrecchia, Alain Mauviel, INSERM U697, Paris 75010, France

Author contributions: All authors contributed equally to the work.

Correspondence to: Franck Verrecchia, INSERM U697, Hôpital Saint-Louis, Pavillon Bazin, 1 avenue Claude Vellefaux, Paris 75010, France. rf.mresni.siuolts@aihccerrev.kcnarf

Telephone: +33-1-53722076 Fax: +33-1-53722051

Franck Verrecchia, Alain Mauviel, INSERM U697, Paris 75010, France

Author contributions: All authors contributed equally to the work.

Correspondence to: Franck Verrecchia, INSERM U697, Hôpital Saint-Louis, Pavillon Bazin, 1 avenue Claude Vellefaux, Paris 75010, France. rf.mresni.siuolts@aihccerrev.kcnarf

Telephone: +33-1-53722076 Fax: +33-1-53722051

Received 2006 Dec 15; Revised 2007 Jan 3; Accepted 2007 Feb 14.

Abstract

Transforming growth factor-β (TGF-β), a prototype of multifunctional cytokine, is a key regulator of extracellular matrix (ECM) assembly and remodeling. Specifically, TGF-β isoforms have the ability to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. Elevated TGF-β expression in affected organs, and subsequent deregulation of TGF-β functions, correlates with the abnormal connective tissue deposition observed during the onset of fibrotic diseases. During the last few years, tremendous progress has been made in the understanding of the molecular aspects of intracellular signaling downstream of the TGF-β receptors. In particular, Smad proteins, TGF-β receptor kinase substrates that translocate into the cell nucleus to act as transcription factors, have been studied extensively. The role of Smad3 in the transcriptional regulation of typeIcollagen gene expression and in the development of fibrosis, demonstrated both in vitro and in animal models with a targeted deletion of Smad3, is of critical importance because it may lead to novel therapeutic strategies against these diseases. This review focuses on the mechanisms underlying Smad modulation of fibrillar collagen expression and how it relates to fibrotic processes.

Keywords: Collagen, Connective tissue growth factor, Fibrosis, Smad, Transforming growth factor-β

Abstract

Footnotes

Supported by Programme National de Recherche Dermatologie 2006, Institut Nationale de la Santé Et de la Recherche Médicale, Groupe Français de Recherche sur la Sclérodermie, and Association des Slérodermiques de France

S- Editor Liu Y L- Editor Alpini GD E- Editor Ma WH

Footnotes

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