Cellular and Molecular Life Sciences

, Volume 68, Issue 5, pp 877–892 | Cite as

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 Article

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.

Keywords

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

Abbreviations

AJC

Apical junctional complex

AJ

Adherens junctions

CDH

Cadherin

CGN

Cingulin

CLDN

Claudin

COPD

Chronic obstructive pulmonary disease

CSE

Cigarette smoke extract

GO

Gene ontology

IAJC

Small airway epithelium apical junctional complex gene expression index

PCA

Principal component analysis

PTEN

Phosphatase and tensin homolog

SAE

Small airway epithelium

TJ

Tight junctions

TJP

Tight junction protein

Notes

Acknowledgments

We thank R.J. Kaner, A.E. Tilley, M.W. Butler, M. O’Mahony, B. Witover and B. Ferris for help with this study, and N. Mohamed for help in preparing the manuscript. These studies were supported, in part, by NIH R01 HL074326; P50 HL084936 and UL1-RR024996.

Supplementary material

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Supplementary material 1 (TIFF 336 kb)
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18_2010_500_MOESM5_ESM.pdf (186 kb)
Supplementary material 5 (PDF 186 kb)
18_2010_500_MOESM6_ESM.doc (56 kb)
Supplementary material 6 (DOC 56 kb)

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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Renat Shaykhiev
    • 1
  • Fouad Otaki
    • 2
  • Prince Bonsu
    • 1
  • David T. Dang
    • 1
  • Matthew Teater
    • 1
  • Yael Strulovici-Barel
    • 1
  • Jacqueline Salit
    • 1
  • Ben-Gary Harvey
    • 1
    • 2
  • Ronald G. Crystal
    • 1
    • 2
  1. 1.Department of Genetic MedicineWeill Cornell Medical CollegeNew YorkUSA
  2. 2.Division of Pulmonary and Critical Care Medicine, Department of MedicineWeill Cornell Medical CollegeNew YorkUSA

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