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01.12.2015 | Research article | Ausgabe 1/2015 Open Access

BMC Pulmonary Medicine 1/2015

Protocadherin-1 is a glucocorticoid-responsive critical regulator of airway epithelial barrier function

Zeitschrift:
BMC Pulmonary Medicine > Ausgabe 1/2015
Autoren:
Yutaka Kozu, Yasuhiro Gon, Shuichiro Maruoka, Kuroda Kazumichi, Akiko Sekiyama, Hiroyuki Kishi, Yasuyuki Nomura, Minoru Ikeda, Shu Hashimoto
Wichtige Hinweise

Competing interests

The author(s) declare that they have no competing interests.

Authors’ contributions

KY and YG contributed equally as co-first authors. YK, YG, SM, KK, and AS performed in vitro cell experiments, data analysis, drafted the paper, and approved its final version. YK, YG, HK, YN, MI, and SH contributed to the study design and clinical study, drafted the paper, and approved its final version.

Abstract

Background

Impaired epithelial barrier function renders the airway vulnerable to environmental triggers associated with the pathogenesis of bronchial asthma. We investigated the influence of protocadherin-1 (PCDH1), a susceptibility gene for bronchial hyperresponsiveness, on airway epithelial barrier function.

Methods

We applied transepithelial electric resistance and dextran permeability testing to evaluate the barrier function of cultured airway epithelial cells. We studied PCDH1 function by siRNA-mediated knockdown and analyzed nasal or bronchial tissues from 16 patients with chronic rhinosinusitis (CRS) and nine patients with bronchial asthma for PCDH1 expression.

Results

PCDH1 was upregulated with the development of epithelial barrier function in cultured airway epithelial cells. Immunocytochemical analysis revealed that PCDH localized to cell-cell contact sites and colocalized with E-cadherin at the apical site of airway epithelial cells. PCDH1 gene knockdown disrupted both tight and adhesion junctions. Immunohistochemical analysis revealed strong PCDH1 expression in nasal and bronchial epithelial cells; however, expression decreased in inflamed tissues sampled from patients with CRS or bronchial asthma. Dexamethasone (Dex) increased the barrier function of airway epithelial cells and increased PCDH1 expression. PCDH1 gene knockdown eradicated the effect of Dex on barrier function.

Conclusion

These results suggest that PCDH1 is important for airway function as a physical barrier, and its dysfunction is involved in the pathogenesis of allergic airway inflammation. We also suggest that glucocorticoids promotes epithelial barrier integrity by inducing PCDH1.
Literatur
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