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E-GEOD-18965 - DECREASED FIBRONECTIN PRODUCTION SIGNIFICANTLY CONTRIBUTES TO DYSREGULATED REPAIR OF ASTHMATIC EPITHELIUM

Status
Submitted on 10 November 2009, released on 12 April 2010, last updated on 2 May 2014
Organism
Homo sapiens
Samples (16)
Array (1)
Protocols (10)
Description
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. 16 arrays, 2 experimental groups, asthma atopic, AA, and healthy non-atopic, HN.
Experiment type
transcription profiling by array 
Contacts
Richard Beyer <dbeyer@u.washington.edu>, Anthony Kicic, Christopher Taplin, Darryl A Knight, Erika N Sutanto, Michael S Kobor, Paul T Stevens, Peter D Paré, Richard P Beyer, Stephen M Stick, Teal S Hallstrand
Citation
Decreased Fibronectin Production Significantly Contributes to Dysregulated Repair of Asthmatic Epithelium. Kicic A, Hallstrand TS, Sutanto EN, Stevens PT, Kobor MS, Taplin C, Paré PD, Beyer RP, Stick SM, Knight DA.
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-18965.idf.txt
Sample and data relationshipE-GEOD-18965.sdrf.txt
Raw data (1)E-GEOD-18965.raw.1.zip
Processed data (1)E-GEOD-18965.processed.1.zip
Array designA-AFFY-33.adf.txt
R ExpressionSetE-GEOD-18965.eSet.r
Links