title: Mouse protocadherin-1 gene expression is regulated by cigarette smoke exposure in vivo.
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.
authors.affiliation: Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Koning
authors.affiliation: Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Antoon J M
authors.initials: AJ
authors.lastname: van Oosterhout
authors.affiliation: Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Uilke
authors.initials: U
authors.lastname: Brouwer
authors.affiliation: Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Lisette E
authors.initials: LE
authors.lastname: den Boef
authors.affiliation: Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Renée
authors.initials: R
authors.lastname: Gras
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Marjan
authors.initials: M
authors.lastname: Reinders-Luinge
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Corry-Anke
authors.initials: CA
authors.lastname: Brandsma
authors.affiliation: Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: van der Toorn
authors.affiliation: Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Machteld N
authors.initials: MN
authors.lastname: Hylkema
authors.affiliation: Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Brigitte W M
authors.initials: BW
authors.lastname: Willemse
authors.affiliation: GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Ian
authors.initials: I
authors.lastname: Sayers
authors.affiliation: Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Koppelman
authors.affiliation: Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands; GRIAC research institute, University of Groningen, University Medical Center Groningen (UMCG), Groningen, the Netherlands.
authors.forename: Martijn C
authors.initials: MC
authors.lastname: Nawijn
mesh_terms: D000818:Animals; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020033:Protein Isoforms / Q000096:biosynthesis; D000091363:Protocadherins; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism*
chemical_list: D015820:Cadherins; C504473:Pcdh1 protein, mouse; D020033:Protein Isoforms; D000091363:Protocadherins