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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-10-30
pubmed:abstractText
We have recently shown that insulin-like growth factor-binding protein (IGFBP)-5 is overexpressed in idiopathic pulmonary fibrosis lung tissues and increases collagen and fibronectin deposition. Here, we further examined the effect of IGFBP-5 in vivo by intratracheal administration of replication-deficient adenovirus expressing human IGFBP-5 (Ad5), IGFBP-3 (Ad3), or no cDNA (cAd) to wild-type mice. Increased cellular infiltration and extracellular matrix deposition were observed in mice after Ad5 administration compared with Ad3 and cAd. Mononuclear cell infiltration consisted predominantly of T lymphocytes at day 8. By day 14, the number of infiltrating T cells decreased, whereas that of B cells and monocytes/macrophages increased. IGFBP-5 also induced migration of peripheral blood mononuclear cells in vitro, suggesting that in vivo mononuclear cell infiltration may be the direct result of IGFBP-5 expression. alpha-Smooth muscle actin and Mucin-1 co-localized in cells of mice treated with Ad5, suggesting that IGFBP-5 induced epithelial-mesenchymal transition. In addition, exogenous IGFBP-5 induced alpha-smooth muscle actin expression in primary fibroblasts and epithelial-mesenchymal transition of pulmonary epithelial cells in vitro. In conclusion, our results suggest that overexpression of IGFBP-5 in mouse lung results in fibroblast activation, increased extracellular matrix deposition, and myofibroblastic changes. Thus, the IGFBP-5-induced fibrotic phenotype in vivo may represent a novel model to better understand the pathogenesis of fibrosis.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-10403273, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-10673212, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-10764308, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-10840790, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-11083266, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-11261778, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-11297318, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-11509325, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-11519507, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-11788658, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-13786180, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-14500651, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-14555542, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15010534, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15286725, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15286810, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15316031, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15501477, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15546457, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15550514, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15681824, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15743780, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15817916, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15855634, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15930103, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-15946381, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-1612128, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-16670278, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-1745844, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-2024710, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-3197813, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-7476973, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-7518191, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-7545694, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-7693664, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-7693840, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-7758431, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-8314838, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-9376117, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-9445300, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-9563754, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-9778216, http://linkedlifedata.com/resource/pubmed/commentcorrection/17071587-9850098
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0002-9440
pubmed:author
pubmed:issnType
Print
pubmed:volume
169
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1633-42
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:17071587-Animals, pubmed-meshheading:17071587-Chemotactic Factors, pubmed-meshheading:17071587-Collagen, pubmed-meshheading:17071587-Epithelial Cells, pubmed-meshheading:17071587-Fibroblasts, pubmed-meshheading:17071587-Fibronectins, pubmed-meshheading:17071587-Humans, pubmed-meshheading:17071587-Inflammation Mediators, pubmed-meshheading:17071587-Insulin-Like Growth Factor Binding Protein 3, pubmed-meshheading:17071587-Insulin-Like Growth Factor Binding Protein 5, pubmed-meshheading:17071587-Leukocytes, Mononuclear, pubmed-meshheading:17071587-Lung, pubmed-meshheading:17071587-Macrophages, pubmed-meshheading:17071587-Mesoderm, pubmed-meshheading:17071587-Mice, pubmed-meshheading:17071587-Mice, Inbred C57BL, pubmed-meshheading:17071587-Phenotype, pubmed-meshheading:17071587-Pulmonary Fibrosis
pubmed:year
2006
pubmed:articleTitle
Insulin-like growth factor-binding protein-5 induces pulmonary fibrosis and triggers mononuclear cellular infiltration.
pubmed:affiliation
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
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