Biomarkers and therapeutic targets: microRNA roles in the pathophysiology, diagnosis and management of eosinophilic esophagitis

Lambert, Kristin; Jhaveri, Punit; Jhaveri, Pooja

doi:10.20517/jtgg.2018.11

Cited by 2 publications

(2 citation statements)

References 39 publications

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“…To validate the results of miRNA expression, we tested them in 15 pairs of biopsies from PPI-R children before and after treatment using qRT-PCR. We analyzed 6 miRNAs upregulated in children after treatment (miR-4485-3p, miR-135a-2-3p, miR-3659, miR-135a-5p, miR-31-3p, and miR-664a-3p) and 11 downregulated miRNAs (miR-520d-5p, miR-520a-5p, miR-525-5p, miR-519d-5p, miR-4773, miR-522-3p, miR-490-3p, miR-137-3p, miR-223-3p, miR-212-5p, and miR-7-5p), which were selected based on several criteria: differential expression with a P value less than 0.05 and a fold change higher than 1.5; putative target genes associated with the pathology; and their implication in the disease, according to previous studies ( 16 ). In addition, we decided to check 2 additional miRNAs: miR-375-3p (Log 2 fold change = 2.17; P value = 0.06) and miR-21-3p (Log 2 fold change = −1.08; P value = 0.09).…”

Section: Resultsmentioning

confidence: 99%

Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis

Cañas

Tabares²,

Barbero

et al. 2020

J. pediatr. gastroenterol. nutr.

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Objectives: Eosinophilic esophagitis (EoE) is a chronic esophageal disease characterized by eosinophilic inflammation. Proton-pump inhibitors (PPI) induce disease remission but no predictive factors of PPI-responsiveness have been identified yet. So, a biomarker must be found to differentiate between responders (PPI-R) and nonresponder patients (PPI-NR) to PPI. Aims were to identify any molecular biomarker that could predict PPI responsiveness and to study molecular remission after PPI therapy. Methods: This prospective study enrolled 39 controls and 43 pediatric children with EoE from 2 hospitals, and they were treated with esomeprazole for 8 to 12 weeks. After therapy, patients were classified as either PPI-R or PPI-NR. Biopsies were collected and RNA, microRNAs, and proteins were isolated from them, measuring levels by qPCR and Western blot (WB). Also, miRNAs were evaluated in serum. Results: We found several esophageal miRNAs with different expression values between PPI-R and PPI-NR children, which can be used to discriminate them (area under curve = 0.90). No useful serum miRNAs were, however, identified. Also, these miRNAs were dysregulated in responder patients before and after PPI therapy. Moreover, we corroborated in this child population, that PPI-R displayed a significant decrease in eotaxin-3, IL-5, IL-13, periostin, and major basic protein ( P < 0.05) and a significant increase in filaggrin levels after PPI treatment ( P < 0.01). Conclusions: Esophageal miRNA levels found are able to discriminate between both PPI-R and PPI-NR at baseline, and before and after treatment in PPI-R, so they could be used as biomarkers. Furthermore, we observed clinical and esophageal molecular restoration in PPI-R patients after PPI therapy.

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Section: Resultsmentioning

confidence: 99%

Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis

Cañas

Tabares²,

Barbero

et al. 2020

J. pediatr. gastroenterol. nutr.

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“…Many of the asthma candidate miRNAs emerged as players in the pathogenesis of atopic dermatitis, suggesting that miRNA pathways may be de-regulated in the skin in an analogous manner to the airways in asthma. Along these lines, Lambert et al [5] reviewed the current literature on miRNAs in eosinophilic esophagitis, a relatively new disease whose pathogenesis is poorly characterized. A panel of miRNAs was found to be de-regulated in inflamed esophageal tissue, and mechanistic studies suggest that they regulate allergic cytokine signaling.…”

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confidence: 99%

Emerging role of MicroRNAs in allergic diseases

Ishmael¹

2019

JTGG

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The prevalence of allergic diseases has risen at alarming rates, and a recent study identified allergic sensitization in 40% of school children worldwide [1] . Allergic diseases affect a wide variety of organs, including eyes (allergic conjunctivitis), nose (allergic rhinitis), airway (asthma), gastrointestinal tract (food allergies and eosinophilic esophagitis), and skin (atopic dermatitis). Common gaps among these diseases are the lack of understanding of the molecular basis of pathogenesis (particularly how and why inflammation is de-regulated), and the crucial need to identify biomarkers to better diagnose and characterize these diseases. Along these lines, microRNAs (miRNAs) have emerged as central regulators of many processes (including inflammation) and potentially useful biomarkers (in large part because they are found in all biofluids). As a result, it is not surprising that these two fields have intersected, and a better understanding of how miRNAs regulate allergic inflammation could lead to novel therapies and diagnostic tools.We are just beginning to understand the roles of miRNAs in allergic diseases. This special issue highlights the emerging roles of miRNAs in across a spectrum of allergic disease that affects different organ systems, and demonstrates their potential application to understanding, treating, and diagnosing human disease. The article by Weidner et al. [2] reviews the progress in our understanding of miRNAs in asthma, and the evolution of research from mouse to humans. This review captures the translational research potential of miRNAs in asthma, and underscores the need for both mouse and human studies in mechanistic miRNA studies. In particular, ablation of pathogenic miRNAs (such as miR-155) in mice has demonstrated their crucial role in pathogenesis of allergic inflammation, and their conserved role in human disease is now becoming evident. In work from our lab, Zhang et al. [3] present a primary research article that builds on the mechanistic studies to show how miRNAs can be used to better characterize asthma. We now understand that asthma is a syndrome that is comprised of many distinct phenotypes, which have different molecular

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Biomarkers and therapeutic targets: microRNA roles in the pathophysiology, diagnosis and management of eosinophilic esophagitis

Cited by 2 publications

References 39 publications

Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis

Proton‐pump Inhibitor Response Prediction Using Esophageal microRNAs in Children With Eosinophilic Esophagitis

Emerging role of MicroRNAs in allergic diseases

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