Publications (2)72.56 Total impact
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Article: Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema.
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ABSTRACT: 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.Nature 04/2003; 422(6928):169-73. · 36.28 Impact Factor -
Article: Loss of integrin v6-mediated TGF- activation causes Mmp12-dependent emphysema
[show abstract] [hide abstract]
ABSTRACT: Integrins are heterodimeric cell-surface proteins that regulate cell growth, migration and survival. We have shown previously that the epithelial-restricted integrinNature 03/2003; 422(6928):169-173. · 36.28 Impact Factor
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- Nature (2)
Institutions
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2003
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National Cancer Institute (USA)
Bethesda, MD, USA
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