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| Status |
Public on Jun 27, 2011 |
| Title |
Smoking-induced Disarray of the Apical Junctional Complex Gene Expression Architecture in the Human Airway Epithelium |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The apical junctional complex (AJC), composed of tight junctions and adherens junctions, is essential for maintaining epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are both associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating AJC integrity in the small airway epithelium (SAE), the primary site of pathological changes in COPD. Transcriptome analysis revealed a global down-regulation of physiological AJC gene expression in the SAE of healthy smokers (n=53) compared to healthy nonsmokers (n=59), an observation associated with changes in molecular pathways regulating epithelial differentiation such as PTEN signaling and accompanied by induction of cancer-related AJC genes. Genome-wide co-expression analysis identified a smoking-sensitive AJC transcriptional network. The overall expression of AJC-associated genes was further decreased in COPD smokers (n=23). Exposure of human airway epithelial cells to cigarette smoke extract in vitro resulted in down-regulation of several AJC-related genes, accompanied by decreased transepithelial resistance. Thus, cigarette smoking alters the AJC gene expression architecture in the human airway epithelium, providing a molecular basis for the dysregulation of airway epithelial barrier function during the development of smoking-induced lung disease.
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| Overall design |
The apical junctional complex (AJC), composed of tight junctions and adherens junctions, is essential for maintaining epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are both associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating AJC integrity in the small airway epithelium (SAE), the primary site of pathological changes in COPD. In this study, microarray analysis of the SAE obtained from 53 healthy nonsmokers, 59 healthy smokers, and 23 smokers with COPD was performed to determine physiological AJC gene expression architecture in the SAE and its modification by cigarette smoking and during the development of COPD.
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| Contributor(s) |
Shaykhiev R, Otaki F, Bonsu P, Dang DT, Teater M, Strulovici-Barel Y, Salit J, Harvey B, Crystal RG |
| Citation(s) |
20820852 |
| |
| Submission date |
Feb 10, 2010 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Yael Strulovici-Barel |
| E-mail(s) |
yas2003@med.cornell.edu
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| Organization name |
Weill Cornell Medical College
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| Department |
Department of Genetic Medicine
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| Lab |
Crystal
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| Street address |
1300 York Avenue
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10021 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (135)
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| GSM101095 |
small airways, non-smoker 001, RMA and MAS |
| GSM101096 |
small airways, non-smoker 004, RMA and MAS |
| GSM101097 |
small airways, non-smoker 002, RMA and MAS |
| GSM101098 |
small airways, non-smoker 003, RMA and MAS |
| GSM101100 |
small airways, non-smoker 006, RMA and MAS |
| GSM101101 |
small airways, non-smoker 021, RMA and MAS |
| GSM101102 |
small airways, non-smoker 019, RMA and MAS |
| GSM101103 |
small airways, non-smoker 014, RMA and MAS |
| GSM101104 |
small airways, non-smoker 008, RMA and MAS |
| GSM101105 |
small airways, non-smoker 015, RMA and MAS |
| GSM101106 |
small airways, non-smoker 005, RMA and MAS |
| GSM101107 |
small airways, smoker 002, RMA and MAS |
| GSM101111 |
small airways, smoker 001, RMA and MAS |
| GSM101113 |
small airways, smoker 048, RMA and MAS |
| GSM101114 |
small airways, smoker 041, RMA and MAS |
| GSM101115 |
small airways, smoker 044, RMA and MAS |
| GSM101116 |
small airways, smoker 049, RMA and MAS |
| GSM114089 |
small airways, smoker 058, MAS5 |
| GSM114090 |
small airways, smoker 063, MAS5 |
| GSM190149 |
Small airways, non-smoker 011 |
| GSM190150 |
Small airways, non-smoker 029 |
| GSM190151 |
small airways, non-smoker 034 |
| GSM190152 |
Small airways, non-smoker 035 |
| GSM190153 |
Small airways, non-smoker 036 |
| GSM190154 |
Small airways, non-smoker 040 |
| GSM190155 |
Small airways, non-smoker 042 |
| GSM190156 |
small airways, non-smoker 044 |
| GSM252828 |
small airways, COPD 008 |
| GSM252829 |
small airways, COPD 012 |
| GSM252830 |
small airways, COPD 014 |
| GSM252831 |
small airways, COPD 015 |
| GSM252833 |
small airways, COPD 036 |
| GSM252835 |
small airways, COPD 046 |
| GSM252836 |
small airways, COPD 059 |
| GSM252837 |
small airways, COPD 068 |
| GSM252838 |
small airways, COPD 074 |
| GSM252839 |
small airways, COPD 080 |
| GSM252841 |
small airways, COPD 103 |
| GSM252871 |
small airways, smoker 040 |
| GSM252876 |
small airways, smoker 057 |
| GSM252879 |
small airways, smoker 074 |
| GSM252880 |
small airways, smoker 093 |
| GSM252881 |
small airways, smoker 094 |
| GSM252882 |
small airways, smoker 095 |
| GSM252884 |
small airways, smoker 098 |
| GSM252885 |
small airways, smoker 103 |
| GSM254149 |
small airways, non-smoker 045 |
| GSM254150 |
small airways, non-smoker 059 |
| GSM254151 |
small airways, non-smoker 071 |
| GSM254152 |
small airways, non-smoker 078 |
| GSM254157 |
small airways, smoker 112 |
| GSM254158 |
small airways, smoker 114 |
| GSM254159 |
small airways, smoker 119 |
| GSM254160 |
small airways, smoker 152 |
| GSM254161 |
small airways, smoker 169 |
| GSM254163 |
small airways, COPD 024 |
| GSM254169 |
small airways, COPD 093 |
| GSM254172 |
small airways, COPD 110 |
| GSM254173 |
small airways, COPD 114 |
| GSM254174 |
small airways, COPD 119 |
| GSM254175 |
small airways, COPD 122 |
| GSM254176 |
small airways, COPD 134 |
| GSM298219 |
small airways, non-smoker 039 |
| GSM298220 |
small airways, non-smoker 046 |
| GSM298221 |
small airways, non-smoker 047 |
| GSM298222 |
small airways, non-smoker 048 |
| GSM298223 |
small airways, non-smoker 050 |
| GSM298224 |
small airways, non-smoker 055 |
| GSM298225 |
small airways, non-smoker 065 |
| GSM298226 |
small airways, non-smoker 072 |
| GSM298227 |
small airways, non-smoker 076 |
| GSM298228 |
small airways, non-smoker 080 |
| GSM298229 |
small airways, non-smoker 083 |
| GSM298230 |
small airways, smoker 087 |
| GSM298231 |
small airways, smoker 102 |
| GSM298232 |
small airways, smoker 120 |
| GSM298233 |
small airways, smoker 122 |
| GSM298234 |
small airways, smoker 123 |
| GSM298235 |
small airways, smoker 125 |
| GSM298236 |
small airways, smoker 129 |
| GSM298237 |
small airways, smoker 130 |
| GSM298238 |
small airways, smoker 134 |
| GSM298239 |
small airways, smoker 136 |
| GSM298240 |
small airways, smoker 141 |
| GSM298241 |
small airways, smoker 155 |
| GSM298242 |
small airways, smoker 159 |
| GSM298243 |
small airways, smoker 161 |
| GSM298244 |
small airways, smoker 164 |
| GSM298245 |
small airways, smoker 167 |
| GSM298246 |
small airways, smoker 176 |
| GSM298247 |
small airways, smoker 177 |
| GSM300859 |
small airways, non-smoker 085 |
| GSM302396 |
small airways, non-smoker 022 |
| GSM302397 |
small airways, non-smoker 066 |
| GSM302399 |
small airways, smoker 195 |
| GSM350871 |
small airways, non-smoker 094 |
| GSM350873 |
small airways, non-smoker 103 |
| GSM350874 |
small airways, smoker 188 |
| GSM350955 |
small airways, non-smoker 110 |
| GSM350956 |
small airways, non-smoker 118 |
| GSM350957 |
small airways, smoker 208 |
| GSM350958 |
small airways, smoker 246 |
| GSM364037 |
small airways, COPD 130 |
| GSM364038 |
small airways, COPD 136 |
| GSM364041 |
small airways, COPD 162 |
| GSM364045 |
small airways, COPD 176 |
| GSM364046 |
small airways, smoker 226 |
| GSM364048 |
small airways, smoker 240 |
| GSM410161 |
small airways, non-smoker 124 |
| GSM410162 |
small airways, non-smoker 138 |
| GSM410163 |
small airways, non-smoker 141 |
| GSM410164 |
small airways, smoker 241 |
| GSM410165 |
small airways, smoker 264 |
| GSM434049 |
small airways, non-smoker 109 |
| GSM434050 |
small airways, non-smoker 119 |
| GSM434051 |
small airways, non-smoker 128 |
| GSM434052 |
small airways, non-smoker 137 |
| GSM434053 |
small airways, smoker 216 |
| GSM434054 |
small airways, smoker 229 |
| GSM434055 |
small airways, smoker 247 |
| GSM434056 |
small airways, smoker 256 |
| GSM434057 |
small airways, smoker 271 |
| GSM434058 |
small airways, smoker 272 |
| GSM434059 |
small airways, smoker 275 |
| GSM434060 |
small airways, smoker 302 |
| GSM434061 |
small airways, smoker 303 |
| GSM434062 |
small airways, smoker 314 |
| GSM434063 |
small airways, smoker 317 |
| GSM434064 |
small airways, COPD 094_2 |
| GSM458579 |
small airways, non-smoker 132 |
| GSM458580 |
small airways, non-smoker 155 |
| GSM458581 |
small airways, non-smoker 163 |
| GSM458582 |
small airways, non-smoker 169 |
| GSM469991 |
small airways, non-smoker 147 |
| GSM470000 |
small airways, smoker 206 |
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| Relations |
| BioProject |
PRJNA124219 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE20257_RAW.tar |
2.8 Gb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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