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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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Public Library of Science
2014
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| Online Access: | https://eprints.nottingham.ac.uk/32632/ |
| _version_ | 1848794453369683968 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Koning, Henk |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-14T19:16:26Z |
| format | Article |
| id | nottingham-32632 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:16:26Z |
| publishDate | 2014 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-326322020-05-04T16:51:28Z https://eprints.nottingham.ac.uk/32632/ 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. 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. Public Library of Science 2014-07-03 Article PeerReviewed 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. and Nawijn, Martijn C. (2014) Mouse Protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo. PLoS ONE, 9 (7). e98197/1-e98197/10. ISSN 1932-6203 http://dx.doi.org/10.1371/journal.pone.0098197 doi:10.1371/journal.pone.0098197 doi:10.1371/journal.pone.0098197 |
| spellingShingle | 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. Mouse Protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo |
| title | 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_short | 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 |
| url | https://eprints.nottingham.ac.uk/32632/ https://eprints.nottingham.ac.uk/32632/ https://eprints.nottingham.ac.uk/32632/ |