Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo.
| Publication Type | Academic Article |
| Authors | Shaykhiev R, Otaki F, Bonsu P, Dang D, Teater M, Strulovici-Barel Y, Salit J, Harvey B, Crystal R |
| Journal | Cell Mol Life Sci |
| Volume | 68 |
| Issue | 5 |
| Pagination | 877-92 |
| Date Published | 09/06/2010 |
| ISSN | 1420-9071 |
| Keywords | Down-Regulation, Epithelial Cells, Intercellular Junctions, Respiratory Mucosa, Smoking, Transcription, Genetic |
| 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. |
| DOI | 10.1007/s00018-010-0500-x |
| PubMed ID | 20820852 |
| PubMed Central ID | PMC3838912 |