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

BMC Pulmonary Medicine

Shu Hashimoto²  Minoru Ikeda³  Yasuyuki Nomura³  Hiroyuki Kishi³  Akiko Sekiyama²  Kuroda Kazumichi¹  Shuichiro Maruoka²  Yasuhiro Gon²  Yutaka Kozu² 

[1] Nihon University School of Medicine Division of Microbiology, 30-1 Ohyaguchi-Kamicho, Itabashiku 173-8610, Tokyo, Japan;Nihon University School of Medicine Division of Respiratory Disease, 30-1 Ohyaguchi-Kamicho, Itabashiku 173-8610, Tokyo, Japan;Nihon University School of Medicine Division of Otolaryngology, 30-1 Ohyaguchi-Kamicho, Itabashiku 173-8610, Tokyo, Japan

关键词: E-cadherin;    Tight junction;    Bronchial hyperresponsiveness;    Corticosteroids;    Airway barrier function;    Chronic rhinosinusitis;    Bronchial asthma;    PCDH1;   

Others  :  1222567
DOI  :  10.1186/s12890-015-0078-z

 received in 2015-01-17, accepted in 2015-07-20,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Kozu et al.

【 图 表 】

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