Functional characterization of the matrix metalloproteinase-1 cigarette smoke-responsive region and association with the lung health study.
Respir Res
; 13: 79, 2012 Sep 19.
Article
em En
| MEDLINE
| ID: mdl-22992122
ABSTRACT
BACKGROUND:
Prior studies have demonstrated that the distal 1.5 kb of the MMP-1 promoter is fundamental in directing the induction of the MMP-1 gene by cigarette smoke.METHODS:
To characterize the genetic variants in the MMP-1 cigarette smoke-responsive element, deep re-sequencing of this element was performed on DNA samples from participants in the Lung Health Study. Furthermore, evidence of Sp1 binding to the MMP-1 promoter was assessed using chromatin immunoprecipitation assays and the influence of cigarette smoke exposure on this interaction was evaluated in cultured human small airway epithelial cells.RESULTS:
Ten polymorphisms (four novel) were detected in the cigarette smoke-responsive element. Chromatin immunoprecipitation assays to assess the protein-DNA interactions at Sp1 sites in the MMP-1 promoter showed increased binding to the Sp1 sites in the cigarette smoke-responsive element in small airway epithelial cells treated with cigarette smoke extract. In contrast, a Sp1 site outside of the element exhibited the opposite effect. None of the polymorphisms were more prevalent in the fast decliners versus the slow decliners (fast decliners = mean -4.14% decline in FEV1% predicted per year vs. decline in FEV1% predicted per year).CONCLUSIONS:
Sequencing analyses identified four novel polymorphisms within the cigarette smoke-responsive element of the MMP-1 promoter. This study identifies functional activity within the cigarette smoke-responsive element that is influenced by cigarette smoke and examines this region of the promoter within a small patient population.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
DNA
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Fumar
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Regiões Promotoras Genéticas
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Metaloproteinase 1 da Matriz
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Polimorfismo de Nucleotídeo Único
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Doença Pulmonar Obstrutiva Crônica
Tipo de estudo:
Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article