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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-9-7
pubmed:abstractText
Pulmonary fibrosis has high rates of mortality and morbidity, but there is no established therapy at present. We demonstrate here that bleomycin-induced pulmonary fibrosis in mice is ameliorated by intratracheal administration of keratinocyte growth factor (KGF)-expressing adenovirus vector. Progressive pulmonary fibrosis was created by continuous subcutaneous administration of 120 mg/kg of bleomycin subcutaneously using an osmotic pump twice from Day 1 to 7 and Day 29 to 35. The mice initially exhibited subpleural fibrosis and then exhibited advanced fibrosis in the parenchyma of the lungs. These histopathological changes were accompanied by reduced lung compliance (0.041 ± 0.011 versus 0.097 ± 0.004; P < 0.001), reduced messenger expression of surfactant proteins, and reduced KGF messenger expression in the lungs at 4 weeks compared with naive group. Intratracheal instillation of Ad-KGF at 1 week after the first administration of bleomycin increased KGF mRNA expression in the lungs compared with the fibrosis-induced mice that received saline alone. The phenotype was associated with alveolar epithelial cell proliferation, increased pulmonary compliance (0.062 ± 0.005 versus 0.041 ± 0.011; P = 0.023), and decreased mortality (survival rate on Day 56: 68.8% versus 0%; P = 0.002), compared with mice receiving only the saline vehicle. These observations suggest the therapeutic utility of a KGF-expressing adenoviral vector for pulmonary fibrosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1535-4989
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
489-97
pubmed:meshHeading
pubmed-meshheading:21131445-Adenoviridae, pubmed-meshheading:21131445-Animals, pubmed-meshheading:21131445-Antibiotics, Antineoplastic, pubmed-meshheading:21131445-Bleomycin, pubmed-meshheading:21131445-Cell Proliferation, pubmed-meshheading:21131445-Fibroblast Growth Factor 7, pubmed-meshheading:21131445-Gene Therapy, pubmed-meshheading:21131445-Immunohistochemistry, pubmed-meshheading:21131445-Lung, pubmed-meshheading:21131445-Male, pubmed-meshheading:21131445-Mice, pubmed-meshheading:21131445-Mice, Inbred C57BL, pubmed-meshheading:21131445-Phenotype, pubmed-meshheading:21131445-Pulmonary Fibrosis, pubmed-meshheading:21131445-Pulmonary Surfactant-Associated Protein D, pubmed-meshheading:21131445-RNA, Messenger, pubmed-meshheading:21131445-Surface-Active Agents, pubmed-meshheading:21131445-Transforming Growth Factor beta1
pubmed:year
2011
pubmed:articleTitle
Keratinocyte growth factor gene transduction ameliorates pulmonary fibrosis induced by bleomycin in mice.
pubmed:affiliation
Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't