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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 20, 2011 |
| Title |
Smoking-induced Wnt pathway downregulation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The Wnt pathway plays a central role in controlling differentiation of epithelial tissues; when Wnt is on, differentiation is suppressed, but when Wnt is off, differentiation is allowed to proceed. Based on this concept, we hypothesized that expression of key genes in the Wnt pathway are suppressed in the human airway epithelium under the stress of cigarette smoking, a stress associated with dysregulation of the differentiated state of the airway epithelium. For this purpose, HG-U133 Plus 2.0 microarrays were used to assess the expression of Wnt-related genes in the small airway (10th-12th generation) epithelium (SAE) obtained via bronchoscopy and brushing of healthy nonsmokers (n=47), healthy smokers (n=58), and smokers with established COPD (n=22). With expression defined as present in >20% of samples, microarray analysis demonstrated that 35 of 57 known Wnt-related genes are expressed in the adult SAE. Wnt pathway downstream targets β-catenin (p<0.05) and the transcription factor 7-like 1 were down-regulated in healthy smokers, and smokers with COPD, as were a number of Wnt target genes, including VEGFA, CCND1, MMP7, CLDN1, SOX9, RHOU (all p<0.05 compared to healthy nonsmokers). As a mechanism to explain this broad, smoking-induced suppression of the Wnt pathway, we assessed expression of the DKK and SFRP families, extracellular regulators that suppress the Wnt pathway. Among these, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold (p<0.0001) in healthy smokers and 4.9-fold (p<0.0001) in COPD smokers, an observation confirmed by TaqMan Real-time PCR. AT the protein levels, Western analysis demonstrated SFRP2 up-regulation, and immunohistochemistry demonstrated that the smoking-induced SFRP2 upregulation occurred in differentiated ciliated cells. Finally, cigarette smoke extract mediated up-regulation of SFRP2 and downregulation of Wnt target genes in airway epithelial cells in vitro. These observations are consistent with the hypothesis that the Wnt pathway plays a role in airway epithelial cell differentiation in the adult human airway epithelium, with smoking associated with down-regulation of Wnt pathway, contributing to the dysregulation of airway epithelial differentiation observed in the smoking-related airway disorders.
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| Overall design |
Affymetrix arrays were used to assess gene expression data of genes in the Wnt pathway in small airway epithelium obtained by fiberoptic bronchoscopy of 47 healthy non-smokers and 58 healthy smokers and 22 smokers with COPD.
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| Contributor(s) |
Wang R, Wang G, Hassan I, Strulovici-Barel Y, Hackett NR, Crystal RG |
| Citation(s) |
21490961 |
| Submission date |
Dec 10, 2009 |
| 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
|
| Department |
Department of Genetic Medicine
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| Lab |
Crystal
|
| 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 (127)
|
| 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 |
| 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 |
| 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 |
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| Relations |
| BioProject |
PRJNA121779 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE19407_RAW.tar |
2.7 Gb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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