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Distinct microRNA Expression in Human Airway Cells of Asthmatic Donors Identifies a Novel Asthma-associated Gene
Citation:
JARDIM, M. J., L. A. DAILEY, AND D. DIAZ SANCHEZ. Distinct microRNA Expression in Human Airway Cells of Asthmatic Donors Identifies a Novel Asthma-associated Gene. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. American Thoracic Society, New York, NY, 47(4):536-42, (2012).
Impact/Purpose:
Here, we tested the hypothesis that differences between healthy and asthmatic subjects may be a result of distinct miRNA cellular profiles that result in differential regulation of inflammatory genes
Description:
Airway inflammation is the hallmark of asthma and suggests a dysregulation of homeostatic mechanisms. MicroRNAs (miRNAs) are key regulators of gene expression, necessary for the proper function of cellular processes. Here, we tested the hypothesis that differences between healthy and asthmatic subjects may be a result of distinct miRNA cellular profiles that result in differential regulation of inflammatory genes. We collected human bronchial epithelial cells from 7 healthy and 7 asthmatic donors and identified 66 miRNAs that were significantly different ( ≤1.5 fold; p-values≤O.05)between the two groups and validated three of them in epithelial cells from 16 asthmatic and 16 healthy subjects. Molecular network analysis indicated that putative targets were principally involved in regulating the expression of inflammatory pathway genes (p-value ≤1O-4).We confirmed the analysis prediction that expression of IL8, Cox2 and TNF-was up-regulated in asthmatic cells while IL6 was lower compared to healthy controls. Network analysis was also used to identify a novel asthma associated gene. The top ranked predicted target of the highly down regulated miR-203 in asthmatic cells was AQP4, an aquaporin gene. Its expression was confirmed to be significantly higher in cells from asthmatic. These data suggest that the heightened inflammatory pathway activation observed in asthmatics may be attributed to underlying aberrant miRNA expression.
