Linked Life Data

11254537

Source:http://linkedlifedata.com/resource/pubmed/id/11254537

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3 Pt 1
pubmed:dateCreated
2001-3-20
pubmed:abstractText
Pulmonary fibrosis is a chronic progressive disease with no effective therapy. Transforming growth factor beta (TGF-beta) is thought to be a key profibrotic mediator and blocking its activity is therefore one of the targets of new treatment strategies for fibrosis. Decorin is an endogenous proteoglycan and one of the known inhibitors of TGF-beta. The short half-life of peptide-based therapeutics makes gene transfer a promising approach to achieve prolonged protein levels in the lung. Replication-deficient adenovirus was used to deliver decorin transgene (AdDec) to the airways by a single intranasal injection in a murine bleomycin model of lung fibrosis. The ability of vector-derived decorin to inhibit TGF-beta was examined in a bioassay and its effect on bleomycin-induced pulmonary fibrosis was determined by histomorphology and lung hydroxyproline. In vitro, supernatant from cells infected with AdDec abrogated the bioactivity of TGF-beta in a dose-dependent manner whereas control virus (AdDL70) had no effect. In vivo, treatment of bleomycin-injected mice with AdDec substantially reduced the fibrogenic response compared with control virus (hydroxyproline: bleomycin/AdDec, 1.96 microg/mg; bleomycin/AdDL70, 3.05 microg/mg; p = 0.0005). These results suggest that a single administration of AdDec was able to generate a local pulmonary environment that effectively blocked the fibrogenic response to bleomycin by inhibition of TGF-beta.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1073-449X
pubmed:author
pubmed:issnType
Print
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
770-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Transient transgene expression of decorin in the lung reduces the fibrotic response to bleomycin.
pubmed:affiliation
Department of Pathology and Molecular Medicine and Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't