Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo.
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.
Shaykhiev
Renat
R
Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
Otaki
Fouad
F
Bonsu
Prince
P
Dang
David T
DT
Teater
Matthew
M
Strulovici-Barel
Yael
Y
Salit
Jacqueline
J
Harvey
Ben-Gary
BG
Crystal
Ronald G
RG
D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020869:Gene Expression Profiling; D006801:Humans; D007365:Intercellular Junctions / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010539:Permeability; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020545:Respiratory Mucosa / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects*; D014158:Transcription, Genetic / Q000187:drug effects*
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