MicroRNA Targets for Asthma Therapy

PLoS ONE, 2011

Background: miRNAs are now recognized as key regulator elements in gene expression. Although they have been associated with a number of human diseases, their implication in acute and chronic asthma and their association with lung remodelling have never been thoroughly investigated.

World Allergy Organization Journal, 2011

One obstacle to developing an effective therapeutic strategy to treat or prevent asthma is that the fundamental causes of asthma are not totally understood. Asthma is thought to be a chronic T H 2 immune-mediated inflammatory disease. Epigenetic changes are recognized to play a role in the initiation and maintenance of a T H 2 response. MicroRNAs (miRNAs) are key epigenetic regulators of gene expression, and their expression is highly regulated, therefore, deregulation of miRNAs may play an important role in the pathogenesis of asthma. Profiling circulating miRNA might provide the highest specificity and sensitivity to diagnose asthma; similarly, correcting potential defects in the miRNA regulation network may lead to new therapeutic modalities to treat this disease.

Experimental and Therapeutic Medicine, 2017

Asthma is a chronic T helper type 2 (Th2) cell-mediated inflammatory disease characterized by airway hyperresponsiveness (AHR) and airway inflammation. Although the majority of patients with asthma can achieve a good level of control with existing treatments, asthma runs a chronic course and the effectiveness of current treatment is not satisfactory for certain patients. MicroRNAs (miRNAs) are short noncoding RNAs that suppress gene expression at the post-transcriptional level; their role in regulating allergic inflammation remains largely unknown. The present study aimed to explore the role of miRNA-155 in the pathogenesis of asthma and its potential as a target for treatment. The expression of miRNA-155 increased in ovalbumin-sensitized and challenged mice compared with control mice, and lentiviral vector-delivered small interfering (si)RNA targeting miRNA-155 resulted in reduced AHR, airway inflammation and Th2 cytokine production. The data from the present study indicate that miRNA-155 serves an important role in the pathogenesis of asthma, and that lentiviral vector-delivered siRNA targeting miRNA-155 may serve as a novel approach for the treatment of allergic asthma.

BMC Pulmonary Medicine, 2011

Background The role of microRNAs (miRNAs) in regulating gene expression is currently an area of intense interest. Relatively little is known, however, about the role of miRNAs in inflammatory and immunologically-driven disorders. In a mouse model, we have previously shown that miRNAs are potentially important therapeutic targets in allergic asthma, because inhibition of miR-126, one of a small subset of miRNAs

Asthma and Lung Biology [Working Title]

Asthma is a common and chronic inflammatory disease. Pathogenic mechanism underlying asthma is complicated. The inflammatory reactions in asthma have been recognized to involve mast cells, eosinophils, lymphocytes (T cells, B cells), macrophages, and dendritic cells. MicroRNA (miRNA, miR) is a group of small noncoding RNAs with 21-25 nucleotides (nt) in length, which impact biologic responses through the regulation of mRNA transcription and/or translation. MicroRNAs are related to developmental processes of many immunologic diseases. Most studies showed that regulation of miRNAs to their targeting genes appears to play an important role in the development of asthma. This chapter has discussed altered expression of miRNAs in cells and tissues from patients with asthma, in order to better understand the mechanics of pathogenesis of asthma. In addition, the regulation of miRNAs as a novel therapeutic approach will require a deeper understanding of their function and mechanism of action.

PLoS ONE, 2009

Background: Asthma is a common disease characterised by reversible airflow obstruction, bronchial hyperresponsiveness and chronic inflammation, which is commonly treated using corticosteroids such as budesonide. MicroRNAs (miRNAs) are a recently identified family of non-protein encoding genes that regulate protein translation by a mechanism entitled RNA interference. Previous studies have shown lung-specific miRNA expression profiles, although their importance in regulating gene expression is unresolved. We determined whether miRNA expression was differentially expressed in mild asthma and the effect of corticosteroid treatment.

PloS one, 2015

MicroRNAs are post-transcriptional regulators of gene expression that are differentially regulated during development and in inflammatory diseases. A role for miRNAs in allergic asthma is emerging and further investigation is required to determine whether they may serve as potential therapeutic targets. We profiled miRNA expression in murine lungs from an ovalbumin-induced allergic airways disease model, and compared expression to animals receiving dexamethasone treatment and non-allergic controls. Our analysis identified 29 miRNAs that were significantly altered during allergic inflammation. Target prediction analysis revealed novel genes with altered expression in allergic airways disease and suggests synergistic miRNA regulation of target mRNAs. To assess the impacts of one induced miRNA on pathology, we targeted miR-155-5p using a specific antagomir. Antagomir administration successfully reduced miR-155-5p expression with high specificity, but failed to alter the disease phenoty...

2020

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Expert Review of Anti-infective Therapy, 2012

microRNAs are short, non-protein coding RNAs that regulate target gene expression principally by causing translational repression and/or mRNA degradation. miRNAs are involved in most mammalian biological processes and have pivotal roles in controlling the expression of factors involved in basal and stimulus-induced signalling pathways. Considering their central role in the regulation of gene expression, miRNAs represent therapeutic drug targets. Here we describe how miRNAs are involved in the regulation of aspects of innate immunity and inflammation, what happens when this goes awry such as in the chronic inflammatory lung diseases cystic fibrosis and asthma, and discuss the current state-of-the-art of miRNA-targeted therapeutics.

Iranian Journal of Allergy, Asthma and Immunology, 2019

In this study, we first tried to determine whether the expression level of 9 miRNAs in the peripheral blood CD8+ T cells of asthmatic patients varies from that of controls, and secondly, we investigated the effects of fluticasone furoate and vilanterol on the expression level of these miRNAs. Fifteen subjects including 8 healthy individuals and 7 asthmatic patients were included in this study. CD8+T cells were isolated from participants' peripheral blood by a negative selection method using magnetic-activated cell sorting (MACS). The expression of 9 miRNAs was examined between the healthy individuals and asthmatic patients. Then the expression level of 9 miRNAs before and after treatment with the drugs was examined by quantitative real-time PCR. No significant changes in the expression level of 9 miRNAs were observed in asthmatic patients compared to the healthy controls. Fluticasone and vilanterol, in combination, had the greatest effect on miRNA expression. MiR-150 and miR-106...