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| Status |
Public on Dec 16, 2008 |
| Title |
Down-regulation of the Notch Differentiation Pathway in the Airway Epithelium of Normal Smokers and Smokers with COPD |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Down-regulation of the Notch Differentiation Pathway in the Human Airway Epithelium in Normal Smokers and Smokers with Chronic Obstructive Lung Disease
In cigarette smokers, the toxic components of smoke place the epithelium under the constant stress of a variety of mechanisms of injury, with consequent modulation of airway epithelial regeneration and disordered differentiation. Based on the underlying hypothesis that these airway epithelial changes must involve quantitative changes in genes involved with the regulation of differentiation, we assessed the expression of the Notch pathway, a signaling pathway known to play a fundamental role in the embryonic lung as a gatekeeper for differentiation, in the small airway epithelium of non-smokers, normal smokers, and smokers with COPD. Microarray analysis demonstrated that 45 of the 55 Notch pathway-related genes are expressed in the human adult small airway epithelium and TaqMan quantitative PCR confirmed the expression of key genes in the pathway. TaqMan quantitative PCR analysis of the normal small airway epithelium demonstrated that Delta-like ligand 1 is the most highly expressed Notch ligand, Notch2 and 3 the most highly expressed receptor genes, and Hes1 the predominant downstream effector gene. TaqMan PCR was used to compare gene expression in nonsmokers vs healthy smokers vs smokers with COPD. The data show that some key genes in the ligands, receptors and downstream effectors in the Notch pathway are differentially expressed in smokers, with significant downregulation of a greater number of Notch-related genes in smokers with COPD compared to healthy smokers. These observations are consistent with the hypothesis that the Notch pathway, known to play an important role in lung morphogenesis, also likely plays a role in the adult human airway epithelium, with at least some of the Notch pathway gene expression dysregulated in association with smoking and its related disorder, COPD.
Keywords: non-smokers, airway epithelial cells
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| Overall design |
Gene expression in airway epithelial cells of normal non-smokers.
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| Contributor(s) |
Tilley AE, Harvey B, Heguy A, Hackett NR, Crystal RG |
| Citation(s) |
19106307 |
| Submission date |
May 17, 2007 |
| 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 (20)
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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 |
| GSM101099 |
small airways, non-smoker 013, 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 |
| 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 |
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| Relations |
| BioProject |
PRJNA100071 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE7832_RAW.tar |
420.0 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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