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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 .

Mouse Protocadherin-1 Gene Expression Is Regulated by Cigarette Smoke Exposure In Vivo