Regulating the Regulators: microRNA and Asthma (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.
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
Aberrant Expression of Immune-related MicroRNAs in Pediatric Patients with Asthma
International Journal of Molecular and Cellular Medicine (IJMCM), 2020
MicroRNAs (miRNAs) have been implicated as regulatory molecules that could play a considerable role in the pathogenesis of different diseases including asthma. This work aims at exploring the role of miR-146a and miR-106b in the pathogenesis of asthma and their association with asthma severity, IgE, and inflammatory cytokines in asthmatic children. Thirty asthmatic children and twenty age-matched healthy children aged 4-17 years old were enrolled. Expression of plasma miR-146a and miR-106b was measured using quantitative real-time PCR. Plasma levels of interleukin-5 (IL-5) and interleukin-13 (IL-13) were assessed using ELISA. Lung functions were measured by Spirometry. MiR-146a and miR-106b were significantly over-expressed in asthmatic children compared to healthy children. A significant positive correlation between total IgE and both miR-146a and miR-106b was found while no significant correlation could be detected between these miRNAs and asthma severity in asthmatic children. Plasma levels of IL-5 and IL-13 were non-significantly higher in asthmatic children compared to healthy children, and there was no significant correlation between them and both miR-146a and miR-106b expressions in the asthmatic children. The aberrant expression of immune-related miRNAs (miR-146a and miR-106b) and inflammatory cytokines (IL-5 and IL-13) among asthmatic children suggest their probable role in asthma pathogenesis.
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.
Circulating MicroRNAs associated with Bronchodilator Response in Childhood Asthma
Research Square (Research Square), 2023
Rationale: Bronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology. Objective: The purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation. Methods: We used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We ltered the participants into high and low bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N= 277) vs low (N= 278) BDR group. Replication was carried out in the Leukotriene modi er Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identi ed, and pathway enrichment analysis was performed. Results: We identi ed 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR=2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways. Conclusion: MiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our ndings add to the growing body of evidence that miRNAs play a signi cant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients.
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...
Circulating miRNAs-A potential tool to identify severe asthma risk
Background: Identifying patients at risk of severe asthma is vitally important given the disproportionate burden of disease imposed by that state. However, biomarkers to support such needs remain elusive. Methods: In this letter, we assessed whether specific panels of circulating miRNAs (microRNAs) can differentiate between mild and severe asthma patients as well as between healthy subjects and severe asthma patients.
Spotlight on microRNAs in allergy and asthma
2020
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