| http://purl.uniprot.org/citations/12634787 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12634787 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.org/dc/terms/identifier | "doi:10.1038/nature01413"xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/author | "Huang X."xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/author | "Wang Y."xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/author | "Sheppard D."xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/author | "Kaminski N."xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/author | "Shapiro S.D."xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/author | "Dolganov G."xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/author | "Morris D.G."xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/author | "Glick A."xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/name | "Nature"xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/pages | "169-173"xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/title | "Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema."xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://purl.uniprot.org/core/volume | "422"xsd:string |
| http://purl.uniprot.org/citations/12634787 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12634787 |
| http://purl.uniprot.org/citations/12634787 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/12634787 |
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| http://purl.uniprot.org/uniprot/Q9Z0T9#attribution-899C444CA91331F589ADD4541F15714A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12634787 |
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| http://purl.uniprot.org/uniprot/P04202#attribution-6E968A817332F4EFAE940EA79724D091 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/12634787 |
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