Transcriptomics

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DECREASED FIBRONECTIN PRODUCTION SIGNIFICANTLY CONTRIBUTES TO DYSREGULATED REPAIR OF ASTHMATIC EPITHELIUM


ABSTRACT: 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.

ORGANISM(S): Homo sapiens  

SUBMITTER: Paul T Stevens  Michael S Kobor   Anthony Kicic   Richard Beyer   Richard P Beyer   Teal S Hallstrand   Christopher Taplin   Darryl A Knight   Peter D Paré   Stephen M Stick   Erika N Sutanto    

PROVIDER: E-GEOD-18965 | ArrayExpress | 2010-04-12

SECONDARY ACCESSION(S): GSE18965PRJNA121007

REPOSITORIES: GEO, ArrayExpress

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Decreased fibronectin production significantly contributes to dysregulated repair of asthmatic epithelium.

Kicic Anthony A   Hallstrand Teal S TS   Sutanto Erika N EN   Stevens Paul T PT   Kobor Michael S MS   Taplin Christopher C   Paré Peter D PD   Beyer Richard P RP   Stick Stephen M SM   Knight Darryl A DA  

American journal of respiratory and critical care medicine 20100128 9


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 children with asthma fail to heal a wound in vitro.To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma.Airway epithelial cells (AEC) from children with asthma (n = 36), healthy atopic control subjects (n = 23), and healthy nonatopic control subjects (n = 53) were investigat  ...[more]

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