Lu, T.X. et al. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J. Allergy Clin. Immunol. 129, 1064-1075 e1069

Division of Allergy and Immunology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 03/2012; 129(4):1064-75.e9. DOI: 10.1016/j.jaci.2012.01.060
Source: PubMed


The role of microRNAs (miRNAs), a key class of regulators of mRNA expression and translation, in patients with eosinophilic esophagitis (EoE) has not been explored.
We aimed to identify miRNAs dysregulated in patients with EoE and assess the potential of these miRNAs as disease biomarkers.
Esophageal miRNA expression was profiled in patients with active EoE and those with glucocorticoid-induced disease remission. Expression profiles were compared with those of healthy control subjects and patients with chronic (noneosinophilic) esophagitis. Expression levels of the top differentially expressed miRNAs from the plasma of patients with active EoE and patients with EoE remission were compared with those of healthy control subjects.
EoE was associated with 32 differentially regulated miRNAs and was distinguished from noneosinophilic forms of esophagitis. The expression levels of the most upregulated miRNAs (miR-21 and miR-223) and the most downregulated miRNA (miR-375) strongly correlated with esophageal eosinophil levels. Bioinformatic analysis predicted interplay of miR-21 and miR-223 with key roles in the polarization of adaptive immunity and regulation of eosinophilia, and indeed, these miRNAs correlated with key elements of the EoE transcriptome. The differentially expressed miRNAs were largely reversible in patients who responded to glucocorticoid treatment. EoE remission induced a single miRNA (miR-675) likely to be involved in DNA methylation. Plasma analysis of the most upregulated esophageal miRNAs identified miR-146a, miR-146b, and miR-223 as the most differentially expressed miRNAs in the plasma.
We have identified a marked dysregulated expression of a select group of miRNAs in patients with EoE and defined their reversibility with glucocorticoid treatment and their potential value as invasive and noninvasive biomarkers.

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    • "Esophageal miRNA expression profile was investigated by microarray from human esophageal tissues of eosinophilic esophagitis (EoE) patients and controls, where the most upregulated miRNAs were miR-21 and miR-223, and the most downregulated one was miR-375. In the plasma of EoE patients, miR-146a, miR-146b, and miR-223 were upregulated [55]. "
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    ABSTRACT: In the past few years expanding knowledge has been accumulated about the role of microRNAs (miRNAs) not only in hematopoiesis and cancer, but also in inflammatory and infectious diseases. Regarding myeloid cells, our knowledge is relatively insufficient, therefore we intended to collect the available data of miRNA profiles of myeloid cells. In addition to a rather general myeloid regulator miR-223, two other miRNAs seem to be useful subjects in understanding of myeloid miRNA biology: miR-27a and miR-652. We review functions of these three miRNAs and other myeloid miRNAs focusing on their roles in monocytes, neutrophils, eosinophils, basophils and mast cells.
    Full-text · Article · Aug 2014 · BioMed Research International
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    • "We now know that many miRNAs play central roles in post-transcriptional gene regulation. Additionally, expression of specific miRNAs has been linked to various diseases [13-16]. Considerable research has been devoted to understanding regulatory roles of miRNAs in human diseases [17-26], and miRNAs are important biomarkers of several disease processes [27-32] including many cancers [33-43] and cardiovascular [18,44-53], inflammation [54-57], and gastrointestinal diseases [58-60]. "
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    ABSTRACT: Background The most important means of identifying diseases before symptoms appear is through the discovery of disease-associated biomarkers. Recently, microRNAs (miRNAs) have become highly useful biomarkers of infectious, genetic and metabolic diseases in human but they have not been well studied in domestic animals. It is probable that many of the animal homologs of human disease-associated miRNAs may be involved in domestic animal diseases. Here we describe a computational biology study in which human disease miRNAs were utilized to predict orthologous miRNAs in cow, chicken, pig, horse, and dog. Results We identified 287 human disease-associated miRNAs which had at least one 100% identical animal homolog. The 287 miRNAs were associated with 359 human diseases referenced in 2,863 Pubmed articles. Multiple sequence analysis indicated that over 60% of known horse mature miRNAs found perfect matches in human disease-associated miRNAs, followed by dog (50%). As expected, chicken had the least number of perfect matches (5%). Phylogenetic analysis of miRNA precursors indicated that 85% of human disease pre-miRNAs were highly conserved in animals, showing less than 5% nucleotide substitution rates over evolutionary time. As an example we demonstrated conservation of human hsa-miR-143-3p which is associated with type 2 diabetes and targets AKT1 gene which is highly conserved in pig, horse and dog. Functional analysis of AKT1 gene using Gene Ontology (GO) showed that it is involved in glucose homeostasis, positive regulation of glucose import, positive regulation of glycogen biosynthetic process, glucose transport and response to food. Conclusions This data provides the animal and veterinary research community with a resource to assist in generating hypothesis-driven research for discovering animal disease-related miRNA from their datasets and expedite development of prophylactic and disease-treatment strategies and also influence research efforts to identify novel disease models in large animals. Integrated data is available for download at
    Full-text · Article · Jun 2014 · BMC Research Notes
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    • "Moreover, primary esophageal epithelial cells were shown to express TSLP mRNA in response to toll-like receptor 3 signaling, suggesting a possible contribution of TSLP in the inflammation and proliferation occurring in EoE affected esophagi. Furthermore, in a genome-wide microarray expression analysis, Lu et al. (34) identified 32 miRNA specific for EoE. Of these, miRNA-21 and miRNA-223 were the most up-regulated in untreated EoE and were down-regulated upon corticosteroid administration. "
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    ABSTRACT: Eosinophilic esophagitis (EoE) is an emerging disease characterized by esophageal eosinophilia (>15eos/hpf), lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast-cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with transforming growth factor-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE.
    Full-text · Article · May 2014 · Frontiers in Pediatrics
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