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Status |
Public on Mar 31, 2010 |
Title |
DECREASED FIBRONECTIN PRODUCTION SIGNIFICANTLY CONTRIBUTES TO DYSREGULATED REPAIR OF ASTHMATIC EPITHELIUM |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from asthmatic children fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n=36), healthy atopic (n=23) and healthy non-atopic controls (n=53) were investigated by microarray, gene expression and silencing, transcript regulation analysis and ability to close mechanical wounds. Results: Wound repair of AEC from healthy and atopic children were not significantly different and were both faster than AEC from asthmatics. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by qPCR and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in non-asthmatic AEC inhibited wound repair, while addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5’, 2’deoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells.
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Overall design |
16 arrays, 2 experimental groups, asthma atopic, AA, and healthy non-atopic, HN.
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Contributor(s) |
Beyer RP, Kicic A, Hallstrand TS, Sutanto EN, Stevens PT, Kobor MS, Taplin C, Paré PD, Stick SM, Knight DA |
Citation(s) |
20110557 |
Submission date |
Nov 10, 2009 |
Last update date |
Aug 10, 2018 |
Contact name |
James William MacDonald |
E-mail(s) |
jmacdon@uw.edu
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Organization name |
University of Washington
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Department |
Environmental and Occupational Health Sciences
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Street address |
4225 Roosevelt Way NE
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City |
Seattle |
State/province |
WA |
ZIP/Postal code |
98105-6099 |
Country |
USA |
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Platforms (1) |
GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
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Samples (16)
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Relations |
BioProject |
PRJNA121007 |
Supplementary file |
Size |
Download |
File type/resource |
GSE18965_RAW.tar |
46.2 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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