TY - JOUR T1 - Airway epithelial protocadherin-1 expression is regulated by house-dust mite and cigarette smoke exposure in mice JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p770 AU - Martijn Nawijn AU - Henk Koning AU - Uilke Brouwer AU - Lisette den Boef AU - Machteld Hylkema AU - Dirkje Postma AU - Gerard Koppelman AU - Antoon van Oosterhout Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p770.abstract N2 - Recently, we identified Protocadherin-1 (PCDH1) as a novel susceptibility gene for Bronchial Hyperresponsiveness (BHR). PCDH1 is expressed in airway epithelial cells and encodes two isoforms of a protocadherin transmembrane protein. We aim to get insight into PCDH1 function in airway epithelial cells in relation to BHR. Therefore, we analyzed in vivo regulation of Pcdh1 isoforms in lung under basal conditions and in mouse models of short-term cigarette smoke (CS) exposure and house-dust mite (HDM) driven experimental asthma. Pcdh1 gene-structure was investigated by Rapid Amplification of cDNA Ends (RACE). Pcdh1 expression was investigated by qRT-PCR, western blotting and immunohistochemistry using isoform-specific antibodies.We identified a novel isoform of Pcdh1 lacking the transmembrane domain but retaining the intracellular signalling motifs, indicating a novel function as signalling adapter molecule. Bronchial epithelial cells expressed all isoforms of Pcdh1, while airway smooth muscle only expressed the isoforms encoding the signal transduction domains. Surprisingly, Pcdh1 expression was unaffected during HDM-exposures, but increased after termination of the treatment, indicating a putative role in epithelial repair. In strong contrast, Pcdh1 mRNA expression was markedly reduced by CS exposure, as soon as 6 hours after a single exposure. These latter data are especially of interest given the initial identification of linkage to the PCDH1 region in CS-exposed families. We conclude that CS-induced changes in airway epithelium directly affect Pcdh1 expression levels, and hypothesize that PCDH1 regulation contributes to the epithelial response to CS-induced injury. ER -