MicroRNA Profiling in Mucosal Biopsies of Eosinophilic Esophagitis Patients Pre and Post Glucocorticoid Steroid Treatment and Relationship with mRNA Target Expression
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36727 | GEO | 2012/03/23
SECONDARY ACCESSION(S): PRJNA153801
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2012-03-23 | E-GEOD-36727 | biostudies-arrayexpress
Project description:Eosinophlic esophagitis (EoE) is increasely recognized as an antigen-drived disorder. The goal of this study is to reveal the gene expression changes in EoE before and after a successful glucocorticoid steroid treatment. We used microarrays to identify distinct genes involving the pathophysiology of EoE. Esophageal mRNA from the epithelial layers of 5 paired paraffin-embedded biopsies before and after treatment with glucocorticosteroids were harvested and profiled using Affymetrix Human Gene 1.0 ST array to generate differentially regulated mRNA transcripts.
2012-03-23 | E-GEOD-36725 | biostudies-arrayexpress
Project description:Eosinophlic esophagitis (EoE) is increasely recognized as an antigen-drived disorder. The goal of this study is to reveal the miRNA expression changes in EoE before and after a successful glucocorticoid steroid treatment. Total RNA was extracted from the esophageal epithelial layers of 5 paired paraffin-embedded biopsies before and after treatment with glucocorticosteroids using RecoverAll Total Nucleic Acid Extraction Kit for FFPE tissues (Ambion, Austin, TX). Five nanograms of total RNA was reverse-transcribed using the Taqman MicroRNA Reverse Transcription Kit and the Megaplex RT primer Human Pool A (Applied Biosystems). The reverse-transcribed cDNA was then pre-amplified in 12 cycles of PCR using Taqman PreAmp Master Mix and the Megaplex PreAmp primers, Human Pool A (Applied Biosystems). The cDNA’s were then diluted and loaded on to a Taqman Human miRNA Array card A (Platform GPL9731 ; Applied Biosystems), which contains probes for 377 distinct miRNAs. The Array cards were run on an ABI HT7900 qPCR instrument. Ct values were obtained for all miRNAs represented on the cards and fold changes in expression were calculated using the delta delta Ct (ddCt) method.
2012-03-23 | E-GEOD-36726 | biostudies-arrayexpress
Project description:Eosinophlic esophagitis (EoE) is increasely recognized as an antigen-drived disorder. The goal of this study is to reveal the miRNA expression changes in EoE before and after a successful glucocorticoid steroid treatment.
2012-03-23 | GSE36726 | GEO
Project description:Eosinophlic esophagitis (EoE) is increasely recognized as an antigen-drived disorder. The goal of this study is to reveal the gene expression changes in EoE before and after a successful glucocorticoid steroid treatment. We used microarrays to identify distinct genes involving the pathophysiology of EoE.
2012-03-23 | GSE36725 | GEO
Project description:The 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.Esophageal 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.Compared 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.Our findings add to the accumulating body of data defining a regulatory role for miRNA in immune and allergic processes.
| S-EPMC3398046 | biostudies-literature
Project description:Background & aimsEosinophilic esophagitis (EoE) is characterized by medically/surgically-resistant gastroesophageal reflux symptoms and dense squamous eosinophilia. Studies suggest that histologic assessment of esophageal eosinophilia alone cannot reliably separate patients with EoE from those with gastroesophageal reflux disease (GERD). Our goal was to develop an assay to identify EoE patients and perhaps differentiate EoE from other causes of esophageal eosinophilia.MethodsA monoclonal antibody specific for an eosinophil secondary granule protein (eosinophil peroxidase [EPX]) was developed and shown to specifically identify intact eosinophils and detect eosinophil degranulation in formalin-fixed specimens. A histopathologic scoring algorithm was developed to analyze data from patient evaluations; the utility of this algorithm was assessed by using archived esophageal tissues from patients with known diagnoses of EoE and GERD as well as controls from 2 tertiary care centers.ResultsIntraobserver/interobserver blinded evaluations demonstrated a significant difference (P < .001) between scores of samples taken from control subjects, from patients with esophageal eosinophilia who had a diagnosis of EoE, and from patients with GERD (P < .001). This algorithm also was able to identify patients whose clinical course was suggestive of a diagnosis of EoE, but that nonetheless failed to reach the critical threshold number of > or =15 eosinophils in a high-power (40x) microscopy field.ConclusionsA novel immunohistochemical scoring system was developed to address an unmet medical need to differentiate histologic specimens from patients with EoE relative to those with GERD. The availability of a unique anti-EPX-specific monoclonal antibody, combined with the ease/rapidity of this staining method and scoring system, will provide a valuable strategy for the assessment of esophageal eosinophilia.
| S-EPMC2706311 | biostudies-literature
Project description:BackgroundEosinophilic esophagitis (EE) involves marked accumulation of eosinophils in the esophageal mucosa that responds to swallowed fluticasone propionate (FP) in a subset of patients.ObjectivesWe aimed to uncover the mechanism of action of swallowed FP in patients with EE by providing evidence for a topical effect in the esophagus by identifying a molecular signature for FP exposure in vivo.MethodsGlobal microarray expression profiles, immunofluorescence microscopy, and cell signaling in esophageal tissue and cell lines were analyzed.ResultsThirty-two transcripts exhibited altered expression in patients who responded to swallowed FP treatment. Esophageal FK506-binding protein 5 (FKBP51) mRNA levels were increased (P < .05) in FP responders compared with those seen in control subjects and patients with untreated active EE. After FP treatment of esophageal epithelial cells, FKBP51 mRNA and protein levels were increased in a dose- and time-dependent manner by FP treatment in vitro. FP-induced FKBP51 was steroid receptor dependent because RU486 completely inhibited gene and protein induction. The half-life of FKBP51 mRNA was 16 to 18 hours independent of FP treatment. FKBP51 overexpression reduced FP action as assessed by FP inhibition of IL-13-induced eotaxin-3 promoter activity.ConclusionsOur results suggest that swallowed glucocorticoid treatment directly affects esophageal gene expression in patients with EE. In particular, increased FKBP51 transcript levels identify glucocorticoid exposure in vivo and distinguish FP responders from untreated patients with active EE and patients without EE. In addition, FKBP51 reduces glucocorticoid-mediated inhibition of IL-13 signaling in epithelial cells in vitro, suggesting that FKBP51 might influence FP responsiveness. We propose that esophageal FKBP51 levels have diagnostic and prognostic significance in patients with EE.
| S-EPMC2865682 | biostudies-literature
Project description:Eosinophilic esophagitis (EoE) is a chronic atopic disease that has become increasingly prevalent over the past 20 years. A first-line pharmacologic option is topical/swallowed corticosteroids, but these are adapted from asthma preparations such as fluticasone from an inhaler and yield suboptimal response rates. There are no FDA-approved medications for the treatment of EoE, and esophageal-specific drug formulations are lacking. We report the development of two novel esophageal-specific drug delivery platforms. The first is a fluticasone-eluting string that could be swallowed similar to the string test "entero-test" and used for overnight treatment, allowing for a rapid release along the entire length of esophagus. In vitro drug release studies showed a target release of 1 mg/day of fluticasone. In vivo pharmacokinetic studies were carried out after deploying the string in a porcine model, and our results showed a high local level of fluticasone in esophageal tissue persisting over 1 and 3 days, and a minimal systemic absorption in plasma. The second device is a fluticasone-eluting 3D printed ring for local and sustained release of fluticasone in the esophagus. We designed and fabricated biocompatible fluticasone-loaded rings using a top-down, Digital Light Processing (DLP) Gizmo 3D printer. We explored various strategies of drug loading into 3D printed rings, involving incorporation of drug during the print process (pre-loading) or after printing (post-loading). In vitro drug release studies of fluticasone-loaded rings (pre and post-loaded) showed that fluticasone elutes at a constant rate over a period of one month. Ex vivo pharmacokinetic studies in the porcine model also showed high tissue levels of fluticasone and both rings and strings were successfully deployed into the porcine esophagus in vivo. Given these preliminary proof-of-concept data, these devices now merit study in animal models of disease and ultimately subsequent translation to testing in humans.
| S-EPMC7917669 | biostudies-literature
Project description:To review the understanding of the pathogenesis of eosinophilic esophagitis (EoE) and the role of the immune system in the disease process.Peer-reviewed articles on EoE from PubMed searching for "Eosinophilic Esophagitis and fibrosis" in the period of 1995 to 2013.Studies on the clinical and immunologic features, pathogenesis, and management of EoE.Recent work has revealed that thymic stromal lymphopoietin and basophil have an increased role in the pathogenesis of disease. Additional understanding on the role of fibrosis in EoE is emerging.The incidence of EoE is increasing like most atopic disease. Similar to other allergic diseases, EoE is treated with topical steroids and/or allergen avoidance.
| S-EPMC4332835 | biostudies-literature