Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo

Renat Shaykhiev, Fouad Otaki, Prince Bonsu, David T. Dang, Matthew Teater, Yael Strulovici-Barel, Jacqueline Salit, Ben Gary Harvey, Ronald G. Crystal

Research output: Contribution to journalArticle

114 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)877-892
Number of pages16
JournalCellular and Molecular Life Sciences
Volume68
Issue number5
DOIs
StatePublished - Mar 1 2011

Keywords

  • Adherens junctions
  • Airway epithelium
  • Chronic obstructive pulmonary disease
  • Cigarette smoking
  • Epithelial polarity
  • Tight junctions
  • Transcriptional regulation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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  • Cite this

    Shaykhiev, R., Otaki, F., Bonsu, P., Dang, D. T., Teater, M., Strulovici-Barel, Y., Salit, J., Harvey, B. G., & Crystal, R. G. (2011). Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo. Cellular and Molecular Life Sciences, 68(5), 877-892. https://doi.org/10.1007/s00018-010-0500-x