Mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.

Protocadherin-1 (PCDH1) is a novel susceptibility gene for airway hyperresponsiveness, first identified in families exposed to cigarette smoke and is expressed in bronchial epithelial cells. Here, we asked how mouse Pcdh1 expression is regulated in lung structural cells in vivo under physiological c...

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Autores principales:	Henk Koning, Antoon J M van Oosterhout, Uilke Brouwer, Lisette E den Boef, Renée Gras, Marjan Reinders-Luinge, Corry-Anke Brandsma, Marco van der Toorn, Machteld N Hylkema, Brigitte W M Willemse, Ian Sayers, Gerard H Koppelman, Martijn C Nawijn
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a4ca3577b6484344b6266fcf8f1cacbe
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spelling	oai:doaj.org-article:a4ca3577b6484344b6266fcf8f1cacbe2021-11-25T06:09:44ZMouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.1932-620310.1371/journal.pone.0098197https://doaj.org/article/a4ca3577b6484344b6266fcf8f1cacbe2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24992194/?tool=EBIhttps://doaj.org/toc/1932-6203Protocadherin-1 (PCDH1) is a novel susceptibility gene for airway hyperresponsiveness, first identified in families exposed to cigarette smoke and is expressed in bronchial epithelial cells. Here, we asked how mouse Pcdh1 expression is regulated in lung structural cells in vivo under physiological conditions, and in both short-term cigarette smoke exposure models characterized by airway inflammation and hyperresponsiveness and chronic cigarette smoke exposure models. Pcdh1 gene-structure was investigated by Rapid Amplification of cDNA Ends. Pcdh1 mRNA and protein expression was investigated by qRT-PCR, western blotting using isoform-specific antibodies. We observed 87% conservation of the Pcdh1 nucleotide sequence, and 96% conservation of the Pcdh1 protein sequence between men and mice. We identified a novel Pcdh1 isoform encoding only the intracellular signalling motifs. Cigarette smoke exposure for 4 consecutive days markedly reduced Pcdh1 mRNA expression in lung tissue (3 to 4-fold), while neutrophilia and airway hyperresponsiveness was induced. Moreover, Pcdh1 mRNA expression in lung tissue was reduced already 6 hours after an acute cigarette-smoke exposure in mice. Chronic exposure to cigarette smoke induced loss of Pcdh1 protein in lung tissue after 2 months, while Pcdh1 protein levels were no longer reduced after 9 months of cigarette smoke exposure. We conclude that Pcdh1 is highly homologous to human PCDH1, encodes two transmembrane proteins and one intracellular protein, and is regulated by cigarette smoke exposure in vivo.Henk KoningAntoon J M van OosterhoutUilke BrouwerLisette E den BoefRenée GrasMarjan Reinders-LuingeCorry-Anke BrandsmaMarco van der ToornMachteld N HylkemaBrigitte W M WillemseIan SayersGerard H KoppelmanMartijn C NawijnPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e98197 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Henk Koning Antoon J M van Oosterhout Uilke Brouwer Lisette E den Boef Renée Gras Marjan Reinders-Luinge Corry-Anke Brandsma Marco van der Toorn Machteld N Hylkema Brigitte W M Willemse Ian Sayers Gerard H Koppelman Martijn C Nawijn Mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.
description	Protocadherin-1 (PCDH1) is a novel susceptibility gene for airway hyperresponsiveness, first identified in families exposed to cigarette smoke and is expressed in bronchial epithelial cells. Here, we asked how mouse Pcdh1 expression is regulated in lung structural cells in vivo under physiological conditions, and in both short-term cigarette smoke exposure models characterized by airway inflammation and hyperresponsiveness and chronic cigarette smoke exposure models. Pcdh1 gene-structure was investigated by Rapid Amplification of cDNA Ends. Pcdh1 mRNA and protein expression was investigated by qRT-PCR, western blotting using isoform-specific antibodies. We observed 87% conservation of the Pcdh1 nucleotide sequence, and 96% conservation of the Pcdh1 protein sequence between men and mice. We identified a novel Pcdh1 isoform encoding only the intracellular signalling motifs. Cigarette smoke exposure for 4 consecutive days markedly reduced Pcdh1 mRNA expression in lung tissue (3 to 4-fold), while neutrophilia and airway hyperresponsiveness was induced. Moreover, Pcdh1 mRNA expression in lung tissue was reduced already 6 hours after an acute cigarette-smoke exposure in mice. Chronic exposure to cigarette smoke induced loss of Pcdh1 protein in lung tissue after 2 months, while Pcdh1 protein levels were no longer reduced after 9 months of cigarette smoke exposure. We conclude that Pcdh1 is highly homologous to human PCDH1, encodes two transmembrane proteins and one intracellular protein, and is regulated by cigarette smoke exposure in vivo.
format	article
author	Henk Koning Antoon J M van Oosterhout Uilke Brouwer Lisette E den Boef Renée Gras Marjan Reinders-Luinge Corry-Anke Brandsma Marco van der Toorn Machteld N Hylkema Brigitte W M Willemse Ian Sayers Gerard H Koppelman Martijn C Nawijn
author_facet	Henk Koning Antoon J M van Oosterhout Uilke Brouwer Lisette E den Boef Renée Gras Marjan Reinders-Luinge Corry-Anke Brandsma Marco van der Toorn Machteld N Hylkema Brigitte W M Willemse Ian Sayers Gerard H Koppelman Martijn C Nawijn
author_sort	Henk Koning
title	Mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.
title_short	Mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.
title_full	Mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.
title_fullStr	Mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.
title_full_unstemmed	Mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.
title_sort	mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/a4ca3577b6484344b6266fcf8f1cacbe
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Mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.

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