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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6928
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pubmed:dateCreated |
2003-3-13
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pubmed:abstractText |
Integrins are heterodimeric cell-surface proteins that regulate cell growth, migration and survival. We have shown previously that the epithelial-restricted integrin alpha(v)beta6 has another critical function; that is, it binds and activates latent transforming growth factor-beta (TGF-beta). Through a global analysis of pulmonary gene expression in the lungs of mice lacking this integrin (Itgb6 null mice) we have identified a marked induction of macrophage metalloelastase (Mmp12)--a metalloproteinase that preferentially degrades elastin and has been implicated in the chronic lung disease emphysema. Here we report that Itgb6-null mice develop age-related emphysema that is completely abrogated either by transgenic expression of versions of the beta6 integrin subunit that support TGF-beta activation, or by the loss of Mmp12. Furthermore, we show that the effects of Itgb6 deletion are overcome by simultaneous transgenic expression of active TGF-beta1. We have uncovered a pathway in which the loss of integrin-mediated activation of latent TGF-beta causes age-dependent pulmonary emphysema through alterations of macrophage Mmp12 expression. Furthermore, we show that a functional alteration in the TGF-beta activation pathway affects susceptibility to this disease.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin beta Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Integrins,
http://linkedlifedata.com/resource/pubmed/chemical/MMP12 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 12,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/integrin alphavbeta6,
http://linkedlifedata.com/resource/pubmed/chemical/integrin beta6
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
422
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
169-73
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12634787-Aging,
pubmed-meshheading:12634787-Animals,
pubmed-meshheading:12634787-Antigens, Neoplasm,
pubmed-meshheading:12634787-Disease Progression,
pubmed-meshheading:12634787-Disease Susceptibility,
pubmed-meshheading:12634787-Gene Deletion,
pubmed-meshheading:12634787-Humans,
pubmed-meshheading:12634787-Inflammation,
pubmed-meshheading:12634787-Integrin beta Chains,
pubmed-meshheading:12634787-Integrins,
pubmed-meshheading:12634787-Macrophages, Alveolar,
pubmed-meshheading:12634787-Matrix Metalloproteinase 12,
pubmed-meshheading:12634787-Metalloendopeptidases,
pubmed-meshheading:12634787-Mice,
pubmed-meshheading:12634787-Mice, Knockout,
pubmed-meshheading:12634787-Mice, Transgenic,
pubmed-meshheading:12634787-Pulmonary Emphysema,
pubmed-meshheading:12634787-Transforming Growth Factor beta
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pubmed:year |
2003
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pubmed:articleTitle |
Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema.
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pubmed:affiliation |
Lung Biology Center, Department of Medicine, San Francisco General Hospital, San Francisco, California 94143, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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