Abstract
BackgroundThe characterization of miRNAs and their target mRNAs involved in regulation of the immune process is an area of intense research and relatively little is known governing these processes in allergic inflammation. Here we present novel findings defining the miRNA and mRNA transcriptome in eosinophilic esophagitis (EoE), an increasing recognized allergic disorder.MethodsEsophageal epithelial miRNA and mRNA from five paired biopsies pre- and post-treatment with glucocorticosteroids were profiled using Taqman and Affymetrix arrays. Validation was performed on additional paired biopsies, untreated EoE specimens and normal controls. Differentially regulated miRNAs and mRNAs were generated, within which miRNA-mRNA target pairs with high predicted confidence were identified.ResultsCompared to the post-glucocorticoid treated esophageal mucosa, of all the 377 miRNA sequences examined, 32 miRNAs were significantly upregulated and four downregulated in the pre-treated biopsies. MiR-214 was the most upregulated (150 fold) and miR-146b-5b, 146a, 145, 142-3p and 21 were upregulated by at least 10 fold. Out of 12 miRNAs chosen for validation by qRT-PCR, five (miR-214, 146b-5p, 146a, 142-3p and 21) were confirmed and 11 shared the same trend. When the expression of the 12 miRNAs in the EoE mucosa was compared to unrelated normal mucosa, six (miR-214, 146b-5p, 146a, 21, 203, and 489) showed similar significant changes as in the paired samples and 10 of them shared the same trend. In the same five pairs of samples used to profile miRNA, 311 mRNAs were down-regulated and 35 were up-regulated in pre-treated EoE mucosa. Among them, 164 mRNAs were identified as potential targets of differentially regulated miRNAs. Further analysis revealed that immune-related genes, targeted and non-targeted by miRNAs, were among the most important genes involved in the pathogenesis of EoE.ConclusionsOur findings add to the accumulating body of data defining a regulatory role for miRNA in immune and allergic processes.
Highlights
Eosinophilic esophagitis (EoE) is an increasingly recognized antigen-driven disorder of the esophagus occurring in children and adults [1]
Published studies have focused on the eosinophilic esophagitis (EoE) transcriptome and a number of dysregulated genes influencing key cellular players such as eosinophils, lymphocytes, mast cells, esophageal epithelial cells and subepithelial myofibroblasts have been characterized [3,4]
PLoS ONE | www.plosone.org miRNA Profile of Eosinophilic Esophagitis mRNA is complex as each mammalian genome contains several hundred miRNAs, a single miRNA may regulate several mRNAs and each mRNA may be affected by several different miRNAs [6]
Summary
Eosinophilic esophagitis (EoE) is an increasingly recognized antigen-driven disorder of the esophagus occurring in children and adults [1]. Published studies have focused on the EoE transcriptome and a number of dysregulated genes influencing key cellular players such as eosinophils, lymphocytes, mast cells, esophageal epithelial cells and subepithelial myofibroblasts have been characterized [3,4]. MicroRNAs (miRNAs) are small, non-coding 19–25 nucleotide long RNAs that constitute the most abundant class of regulators of gene expression [5]. Their primary mechanism of action is posttranscriptional regulation via RNA interference leading to mRNA strand degradation or translational inhibition. We present novel findings defining the miRNA and mRNA transcriptome in eosinophilic esophagitis (EoE), an increasing recognized allergic disorder
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