Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo Academic Article uri icon

Overview

MeSH Major

  • Down-Regulation
  • Epithelial Cells
  • Intercellular Junctions
  • Respiratory Mucosa
  • Smoking
  • Transcription, Genetic

abstract

  • The apical junctional complex (AJC), composed of tight and adherens junctions, maintains epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating airway epithelial AJC integrity. Transcriptome analysis revealed global down-regulation of physiological AJC gene expression in the airway epithelium of healthy smokers (n = 59) compared to nonsmokers (n = 53) in association with changes in canonical epithelial differentiation pathways such as PTEN signaling accompanied by induction of cancer-related AJC components. The overall expression of AJC-related genes was further decreased in COPD smokers (n = 23). Exposure of airway epithelial cells to cigarette smoke extract in vitro resulted in down-regulation of several AJC genes paralleled by decreased transepithelial resistance. Thus, cigarette smoking induces transcriptional reprogramming of airway epithelial AJC architecture from its physiological pattern necessary for barrier function toward a disease-associated molecular phenotype.

publication date

  • March 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3838912

Digital Object Identifier (DOI)

  • 10.1007/s00018-010-0500-x

PubMed ID

  • 20820852

Additional Document Info

start page

  • 877

end page

  • 92

volume

  • 68

number

  • 5