Document Detail


Transforming growth factors-beta 1, -beta 2, and -beta 3 stimulate fibroblast procollagen production in vitro but are differentially expressed during bleomycin-induced lung fibrosis.
MedLine Citation:
PMID:  9060836     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transforming growth factor (TGF)-beta 1 may potentiate wound healing and fibrosis by stimulating fibroblast collagen deposition. TGF-beta 1 is implicated in the pathogenesis of pulmonary fibrosis, but the role of TGF-beta 2 and TGF-beta 3 remains unclear. We examined their effects on lung fibroblast procollagen metabolism in vitro and localized their gene expression during bleomycin-induced lung fibrosis using in situ hybridization with digoxigenin-labeled riboprobes. All three isoforms stimulated fibroblast procollagen production. TGF-beta 3 was the most potent and also reduced procollagen degradation. In normal mouse lung, TGF-beta 1 and TGF-beta 3 mRNA transcripts were abundant in bronchiolar epithelium. After bleomycin, TGF-beta 1 gene expression was maximally enhanced at 10 days, with the signal being predominant in macrophages. Signal was also enhanced in mesenchymal, pulmonary endothelial, and mesothelial cells. After 35 days, the pattern of TGF-beta 1 gene expression returned to that of control lung. TGF-beta 3 gene expression remained unchanged throughout compared with controls. TGF-beta 2 mRNA was not detected with the antisense probe, but signal obtained with the sense probe suggests the presence of a naturally occurring antisense. This study demonstrates that TGF-beta 1, -beta 2, and -beta 3 all exert profibrotic effects in vitro. However, TGF-beta isoform gene expression is differentially controlled during experimental pulmonary fibrosis with TGF-beta 1 the predominant isoform expressed during pathogenesis.
Authors:
R K Coker; G J Laurent; S Shahzeidi; P A Lympany; R M du Bois; P K Jeffery; R J McAnulty
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of pathology     Volume:  150     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-04-07     Completed Date:  1997-04-07     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  981-91     Citation Subset:  AIM; IM    
Affiliation:
Centre for Cardiopulmonary Biochemistry and Respiratory Medicine, University College London Medical School, United Kingdom.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bleomycin*
Carrier Proteins / genetics*,  pharmacology
Cells, Cultured
Fibroblasts / metabolism*
Fibrosis / chemically induced
Gene Expression
Gene Expression Regulation*
In Situ Hybridization
Intracellular Signaling Peptides and Proteins*
Isomerism
Latent TGF-beta Binding Proteins
Lung / drug effects,  metabolism,  pathology
Mice
Procollagen / biosynthesis*
Pulmonary Fibrosis / chemically induced*,  pathology,  physiopathology*
Transforming Growth Factor beta / genetics*,  pharmacology
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Latent TGF-beta Binding Proteins; 0/Procollagen; 0/Transforming Growth Factor beta; 11056-06-7/Bleomycin
Comments/Corrections

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