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 language | English (US) |
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Pages (from-to) | 877-892 |
Number of pages | 16 |
Journal | Cellular and Molecular Life Sciences |
Volume | 68 |
Issue number | 5 |
DOIs | |
State | Published - Mar 2011 |
Externally published | Yes |
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