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

BMC Pulm Med. 2015 Jul 31;15:80. doi: 10.1186/s12890-015-0078-z.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Asthma / drug therapy
  • Asthma / genetics*
  • Asthma / metabolism
  • Bronchi / drug effects
  • Bronchi / metabolism
  • Bronchi / pathology
  • Cadherins / biosynthesis
  • Cadherins / genetics*
  • Cells, Cultured
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation*
  • Glucocorticoids / pharmacology*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • RNA / genetics*
  • Real-Time Polymerase Chain Reaction
  • Tight Junctions / metabolism
  • Young Adult

Substances

  • Cadherins
  • Glucocorticoids
  • PCDH1 protein, human
  • RNA