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Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo
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Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo
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Journal Article
Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo
2011
Overview
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.
Publisher
Basel : SP Birkhäuser Verlag Basel,SP Birkhäuser Verlag Basel,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ Chronic obstructive pulmonary disease
/ Down-Regulation - drug effects
/ Epithelial Cells - drug effects
/ Epithelial Cells - metabolism
/ Epithelial Cells - ultrastructure
/ Genes
/ Humans
/ Intercellular Junctions - drug effects
/ Intercellular Junctions - genetics
/ Intercellular Junctions - metabolism
/ Oligonucleotide Array Sequence Analysis
/ Pulmonary Disease, Chronic Obstructive - genetics
/ Pulmonary Disease, Chronic Obstructive - metabolism
/ Pulmonary Disease, Chronic Obstructive - pathology
/ Respiratory Mucosa - drug effects
/ Signal Transduction - drug effects
/ Smoking
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