MicroRNAs Profiling in Murine Models of Acute and Chronic Asthma: A Relationship with mRNAs Targets (original) (raw)
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Pathogenic Roles of MicroRNA in the Development of Asthma
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.
Postȩpy dermatologii i alergologii, 2016
The asthma- and chronic obstructive pulmonary disease (COPD)-related morbidity has been increasing during the recent years. Both asthma and COPD are diseases of inflammatory etiology. The increasing interest in the pathomechanisms involved in the development of obstructive pulmonary diseases seems to be fully justified. Recent research has attempted to determine the associations of microRNA with the pathogenesis of pulmonary diseases. To assess the expression of microRNA in the blood sera of patients diagnosed with bronchial asthma and chronic obstructive pulmonary disease in comparison with healthy subjects. In our study, at the preliminary stage, we compared the expression of miRNA in the groups of patients with asthma and COPD versus the control group of healthy subjects. A significant difference in hsa-miRNA-224, hsa-miRNA-339-5p, hsa-miRNA-382 in patients with asthma and COPD as compared with the controls was noted. With such difference of expression of specific micro-RNA in se...
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
MicroRNA Expression Profiling in Mild Asthmatic Human Airways and Effect of Corticosteroid Therapy
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.
Regulating the Regulators: microRNA and Asthma
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.
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...
MicroRNAs—A Promising Tool for Asthma Diagnosis and Severity Assessment: A Systematic Review
Journal of Personalized Medicine, 2022
Micro RNAs (miRNAs) are short, non-coding RNAs (Ribonucleic acids) with regulatory functions that could prove useful as biomarkers for asthma diagnosis and asthma severity-risk stratification. The objective of this systematic review is to identify panels of miRNAs that can be used to support asthma diagnosis and severity-risk assessment. Three databases (Medline, Embase, and SCOPUS) were searched up to 15 September 2020 to identify studies reporting differential expression of specific miRNAs in the tissues of adults and children with asthma. Studies reporting miRNAs associations in animal models that were also studied in humans were included in this review. We identified 75 studies that met our search criteria. Of these, 66 studies reported more than 200 miRNAs that are differentially expressed in asthma patients when compared to non-asthmatic controls. In addition, 16 studies reported 17 miRNAs that are differentially expressed with differences in asthma severity. We were able to c...
Plasma microRNA profiles identify distinct clinical phenotypes in human asthmatics
Journal of Translational Genetics and Genomics, 2018
Aim: Asthma is a chronic inflammatory syndrome that is characterized by heterogeneous disease pathogeneses that produce distinct subtypes. There is a great need to develop biomarkers to distinguish these subtypes and help guide specific therapy and better predict outcomes, particularly in severe asthma where a number of targeted therapeutics are now available. We sought to determine whether expression of asthma-specific microRNAs (miRNAs) could distinguish phenotypic differences in a diverse cohort of asthmatic subjects that spanned a range of disease severity. Methods: RNA was isolated from peripheral blood from human subjects. Expression of 39 miRNAs was then screened. Sample cycle threshold values were normalized. Normally distributed data were analyzed and hierarchical cluster was performed. Results: Peripheral blood was obtained from 62 adults. We identified four clusters of asthmatics defined by 5 distinct miRNA expression patterns. Cluster 1 was associated with mild asthma, low inhaled corticosteroid use, and low eosinophil levels. Cluster 3 and 4 consisted primarily of severe asthmatics with poor asthma control, and Cluster 3 was specifically associated with high IgE, high blood eosinophil levels, and racial disparity (higher proportion of Black subjects). Cluster 2 was comprised predominantly of mild-moderate asthmatics that had higher blood eosinophils than Cluster 1. Conclusion: These results indicate the miRNA expression profiling can be useful to identify distinct asthma phenotypes, and have potential to better understand disease pathogenesis and help guide therapy.
Antagonism of mmu-mir-106a attenuates asthma features in allergic murine model
Journal of Applied Physiology, 2012
MicroRNAs (miRs) regulate immunological pathways in health and disease, and a number of miRs have been shown to be altered in mouse models of asthma. The secretion of interleukin-10 (IL-10), an anti-inflammatory cytokine, has been shown to be defective in many inflammatory diseases including asthma. We recently demonstrated that miR-106a inhibits IL-10 in a post-transcriptional manner. In this study, we investigated the effect of inhibition of mmu-miR106a in asthmatic condition to find its possible role as a therapeutic target. Our in vitro experiments with mouse macrophage, RAW264.7, revealed that mmu-miR-106a potentially decreased IL-10 along with increase in proinflammatory cytokine. Furthermore, administration of mmu-miR-106a to naive mice reduced IL-10 levels in lungs in a dose-dependent manner without altering lung histology. Most interestingly, knockdown of mmu-miR-106a in an established allergic airway inflammation has significantly alleviated most of the features of asthma ...