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Cellular mechanisms underlying CCSP SNP association with chronic airway diseases
- Source :
- 5.1 Airway Pharmacology and Treatment.
- Publication Year :
- 2015
- Publisher :
- European Respiratory Society, 2015.
-
Abstract
- Club cell secretory protein (CCSP) is an endogenous anti-inflammatory product with a protective role in the respiratory tract. Impaired airway homeostasis in chronic bronchial diseases might be related to CCSP G38A polymorphism but the SNP-transcription relationship is not established. This study was to examine the influence of ccsp G38A polymorphism on CCSP expression and regulation. Vectors constructions (proximal promoter: 229bp; and distal promoter: 926bp) containing -38G wild type or the -38A variant were designed. Human bronchial BEAS-2B cells were transfected with these proximal or distal promoters, in presence/absence of cigarette smoke extract (CSE). Dual luciferase assay system reflected CCSP transcription levels. In parallel, dual transfections with candidate modulating transcription factors identified by in silico analysis using ConSite and TFSEARCH were conducted. No significant changes are induced by the -38G and -38A vectors in transiently transfected BEAS-2B cells. Cotransfection with Nkx2.1 significantly increased CCSP transcription. Interestingly, with proximal promoter only,-38A variant gene response to Nkx2.1 was higher than -38G wild type response. CSE decreased CCSP transcription. In depth-in silico analyzes identified two novel candidate transcription factors that could specifically bind to the G38A locus: Thing1E47 and p53. Our data indicate that two novel transcription factors and CSE could affect CCSP expression. Also, -38A variant CCSP gene modulation induced by Nkx2.1 is significant. Finding transcription factors that could restore normal levels of CCSP expression is of interest.
Details
- Database :
- OpenAIRE
- Journal :
- 5.1 Airway Pharmacology and Treatment
- Accession number :
- edsair.doi...........51868ebf73a645ff361f707b548f3578