title: Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo.
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.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
authors.forename: Renat
authors.initials: R
authors.lastname: Shaykhiev
authors.forename: Fouad
authors.initials: F
authors.lastname: Otaki
authors.forename: Prince
authors.initials: P
authors.lastname: Bonsu
authors.forename: David T
authors.initials: DT
authors.lastname: Dang
authors.forename: Matthew
authors.initials: M
authors.lastname: Teater
authors.forename: Yael
authors.initials: Y
authors.lastname: Strulovici-Barel
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Salit
authors.forename: Ben-Gary
authors.initials: BG
authors.lastname: Harvey
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: 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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