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

Koning, Henk; Oosterhout, Antoon J.M. van; Brouwer, Uilke; Boef, Lisette E. den; Gras, Renée; Reinders-Luinge, Marjan; Brandsma, Corry-Anke; Toorn, Marco van der; Hylkema, Machteld N.; Willemse, Brigitte W.M.; Sayers, Ian; Koppelman, Gerard H.; Nawijn, Martijn C.

Authors

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



Abstract

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.

Journal Article Type Article
Publication Date Jul 3, 2014
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 9
Issue 7
Article Number e98197
APA6 Citation Koning, H., Oosterhout, A. J. V., Brouwer, U., Boef, L. E. D., Gras, R., Reinders-Luinge, M., …Nawijn, M. C. (2014). Mouse Protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo. PLoS ONE, 9(7), doi:10.1371/journal.pone.0098197
DOI https://doi.org/10.1371/journal.pone.0098197
Publisher URL http://dx.doi.org/10.1371/journal.pone.0098197
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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