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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2011-8-26
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pubmed:abstractText |
Plasminogen activator inhibitor-1 (PAI-1) is increased in the lungs of patients with pulmonary fibrosis, and animal studies have shown that experimental manipulations of PAI-1 levels directly influence the extent of scarring that follows lung injury. PAI-1 has 2 known properties that could potentiate fibrosis, namely an antiprotease activity that inhibits the generation of plasmin, and a vitronectin-binding function that interferes with cell adhesion to this extracellular matrix protein. To determine the relative importance of each PAI-1 function in lung fibrogenesis, we administered mutant PAI-1 proteins that possessed either intact antiprotease or vitronectin-binding activity to bleomycin-injured mice genetically deficient in PAI-1. We found that the vitronectin-binding capacity of PAI-1 was the primary determinant required for its ability to exacerbate lung scarring induced by intratracheal bleomycin administration. The critical role of the vitronectin-binding function of PAI-1 in fibrosis was confirmed in the bleomycin model using mice genetically modified to express the mutant PAI-1 proteins. We conclude that the vitronectin-binding function of PAI-1 is necessary and sufficient in its ability to exacerbate fibrotic processes in the lung.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Bleomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyproline,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SERPINE1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Serpin E2,
http://linkedlifedata.com/resource/pubmed/chemical/Serpine2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Vitronectin
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1528-0020
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pubmed:author |
pubmed-author:CoureyAnthony JAJ,
pubmed-author:CunninghamAndrew KAK,
pubmed-author:GoldklangMonica PMP,
pubmed-author:HorowitzJeffrey CJC,
pubmed-author:KimKevin KKK,
pubmed-author:KohTimothy JTJ,
pubmed-author:LawrenceDaniel ADA,
pubmed-author:LinYujingY,
pubmed-author:NovakMargaret LML,
pubmed-author:SimonRichard HRH,
pubmed-author:SissonThomas HTH,
pubmed-author:SubbotinaNatalyaN,
pubmed-author:WarnockMarkM,
pubmed-author:XueBingB
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pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
118
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2313-21
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pubmed:meshHeading |
pubmed-meshheading:21734232-Animals,
pubmed-meshheading:21734232-Bleomycin,
pubmed-meshheading:21734232-Bronchoalveolar Lavage Fluid,
pubmed-meshheading:21734232-Collagen,
pubmed-meshheading:21734232-Disease Models, Animal,
pubmed-meshheading:21734232-Humans,
pubmed-meshheading:21734232-Hydroxyproline,
pubmed-meshheading:21734232-Lung,
pubmed-meshheading:21734232-Mice,
pubmed-meshheading:21734232-Mice, Inbred C57BL,
pubmed-meshheading:21734232-Mice, Knockout,
pubmed-meshheading:21734232-Mice, Transgenic,
pubmed-meshheading:21734232-Mutant Proteins,
pubmed-meshheading:21734232-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:21734232-Protein Binding,
pubmed-meshheading:21734232-Pulmonary Fibrosis,
pubmed-meshheading:21734232-Recombinant Proteins,
pubmed-meshheading:21734232-Serpin E2,
pubmed-meshheading:21734232-Vitronectin
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pubmed:year |
2011
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pubmed:articleTitle |
The vitronectin-binding function of PAI-1 exacerbates lung fibrosis in mice.
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pubmed:affiliation |
Division of Pulmonary and Critical Care Medicine. Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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