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PMID: 17589920 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Transforming growth factor-beta and fibrosis.

World journal of gastroenterology ·Vol. 13 ·No. 22 ·2007-06-14 ·Pages 3056-62

Verrecchia F, Mauviel A

Abstract

Transforming growth factor-beta (TGF-beta), a prototype of multifunctional cytokine, is a key regulator of extracellular matrix (ECM) assembly and remodeling. Specifically, TGF-beta 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-beta expression in affected organs, and subsequent deregulation of TGF-beta 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-beta receptors. In particular, Smad proteins, TGF-beta 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 type I collagen 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.

MeSH Terms
Animals Collagen/physiology Connective Tissue/pathology Connective Tissue Growth Factor Extracellular Matrix/physiology Fibrosis/pathology,physiopathology Humans Immediate-Early Proteins/physiology Intercellular Signaling Peptides and Proteins/physiology Receptors, Transforming Growth Factor beta/physiology Skin/pathology,physiopathology Skin Diseases/pathology,physiopathology Smad Proteins/physiology Transforming Growth Factor beta/physiology
Chemicals
CCN2 protein, human Immediate-Early Proteins Intercellular Signaling Peptides and Proteins Receptors, Transforming Growth Factor beta Smad Proteins Transforming Growth Factor beta Connective Tissue Growth Factor Collagen
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Verrecchia Franck
INSERM U697, Hopital Saint-Louis, Pavillon Bazin, 1 avenue Claude Vellefaux, Paris 75010, France. [email protected]
Mauviel Alain
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Article Info
Journal
World journal of gastroenterology
Abbr.
World J Gastroenterol
ISSN
1007-9327
DOI
10.3748/wjg.v13.i22.3056
Email
[email protected]
Published
2007-06-14
Pages
3056-62
Language
English
Region
United States
NLM ID
100883448
PMCID
PMC4172611
Subset
IM
Corrections
CommentIn
PMID: 17589916
External Links
PubMed source DOI: 10.3748/wjg.v13.i22.3056 PMC Full Text View journal details
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