Document Detail

Adenovector-mediated gene transfer of active transforming growth factor-beta1 induces prolonged severe fibrosis in rat lung.
MedLine Citation:
PMID:  9259574     Owner:  NLM     Status:  MEDLINE    
Transforming growth factor (TGF)-beta1 has been implicated in the pathogenesis of fibrosis based upon its matrix-inducing effects on stromal cells in vitro, and studies demonstrating increased expression of total TGF-beta1 in fibrotic tissues from a variety of organs. The precise role in vivo of this cytokine in both its latent and active forms, however, remains unclear. Using replication-deficient adenovirus vectors to transfer the cDNA of porcine TGF-beta1 to rat lung, we have been able to study the effect of TGF-beta1 protein in the respiratory tract directly. We have demonstrated that transient overexpression of active, but not latent, TGF-beta1 resulted in prolonged and severe interstitial and pleural fibrosis characterized by extensive deposition of the extracellular matrix (ECM) proteins collagen, fibronectin, and elastin, and by emergence of cells with the myofibroblast phenotype. These results illustrate the role of TGF-beta1 and the importance of its activation in the pulmonary fibrotic process, and suggest that targeting active TGF-beta1 and steps involved in TGF-beta1 activation are likely to be valuable antifibrogenic therapeutic strategies. This new and versatile model of pulmonary fibrosis can be used to study such therapies.
P J Sime; Z Xing; F L Graham; K G Csaky; J Gauldie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  100     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1997 Aug 
Date Detail:
Created Date:  1997-10-09     Completed Date:  1997-10-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  768-76     Citation Subset:  AIM; IM    
Molecular Virology and Immunology Program, Health Sciences Center, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
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MeSH Terms
Actins / analysis
Adenoviridae / genetics
Collagen / analysis
Elastin / analysis
Fibronectins / analysis
Gene Transfer Techniques
Genetic Vectors
Hydroxyproline / analysis
Lung / metabolism,  pathology
Peptide Fragments*
Protein Precursors*
Proteins / genetics,  metabolism
Pulmonary Fibrosis / etiology*,  pathology
Rats, Sprague-Dawley
Time Factors
Transforming Growth Factor beta / genetics,  physiology*
Transforming Growth Factor beta1
Reg. No./Substance:
0/Actins; 0/Fibronectins; 0/Peptide Fragments; 0/Protein Precursors; 0/Proteins; 0/Transforming Growth Factor beta; 0/Transforming Growth Factor beta1; 51-35-4/Hydroxyproline; 9007-34-5/Collagen; 9007-58-3/Elastin

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