MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase–mediated suppression of histone deacetylase 2

Kim, Richard; Horvat, Jay C.; Pinkerton, James; Starkey, Malcolm R.; Essilfie, Ama-Tawiah; Mayall, Jemma; Nair, Prema M.; Hansbro, Philip M.; Jones, Bernard Edward; Haw, Tatt Jhong; Sunkara, Krishna; Nguyen, Thi Hiep; Jarnicki, Andrew G.; Keely, Simon; Mattes, Joërg; Adcock, Ian M.; Foster, Paul S.

doi:10.1016/j.jaci.2016.04.038

Cited by 187 publications

(225 citation statements)

References 84 publications

(121 reference statements)

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“…92 Our collaborators also recently demonstrated that RSV infection-induced exacerbations increased miR-21 expression. 93 Blocking miR-21 function restored steroid sensitivity in this model and reduced AHR in the presence or absence of steroid treatment. 93 A number of studies have also assessed RV-induced exacerbations in mouse models.…”

Section: Pathogen-induced Exacerbation Viralmentioning

confidence: 79%

“…93 Blocking miR-21 function restored steroid sensitivity in this model and reduced AHR in the presence or absence of steroid treatment. 93 A number of studies have also assessed RV-induced exacerbations in mouse models. It is important to note that due to species differences between human and mouse, 'major group' RV virus cannot infect mouse cells.…”

Section: Pathogen-induced Exacerbation Viralmentioning

confidence: 79%

“…99 Interestingly, blocking miR-21 also suppressed influenza-induced disease exacerbations, suggesting an overlapping mechanism with RSV infection-induced exacerbations. 93 Together, these studies demonstrate that virus infection can exacerbate disease through potentiation of preexisting type-2 immune responses or through activation of innate and/or type-1 inflammatory pathways. Thus, the best intervention strategy to reduce virus infection-induced exacerbation severity will likely depend on the infection context and the preexisting disease phenotype.…”

Section: Pathogen-induced Exacerbation Viralmentioning

confidence: 88%

“…104,105 When animals were allergenchallenged after resolution of Chlamydia infection, increased neutrophil accumulation and T H 1/T H 17-associated gene expression were observed, along with steroid-resistant AHR. 93 This occurred despite reduced eosinophil accumulation and reduced T H 2 responses. 93 Similar to observations in virus infection-induced exacerbation, miR-21 expression was also increased in this model and blocking miR-21 reduced AHR.…”

Section: Bacterialmentioning

confidence: 98%

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Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation

et al. 2017

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Severe asthma has significant disease burden and results in high healthcare costs. While existing therapies are effective for the majority of asthma patients, treatments for individuals with severe asthma are often ineffective. Mouse models are useful to identify mechanisms underlying disease pathogenesis and for the preclinical assessment of new therapies. In fact, existing mouse models have contributed significantly to our understanding of allergic/eosinophilic phenotypes of asthma and facilitated the development of novel targeted therapies (e.g. anti-IL-5 and anti-IgE). These therapies are effective in relevant subsets of severe asthma patients. Unfortunately, non-allergic/noneosinophilic asthma, steroid resistance and disease exacerbation remain areas of unmet clinical need. No mouse model encompasses all features of severe asthma. However, mouse models can provide insight into pathogenic pathways that are relevant to severe asthma. In this review, as examples, we highlight models relevant to understanding steroid resistance, chronic tissue remodelling and disease exacerbation. Although these models highlight the complexity of the immune pathways that may underlie severe asthma, they also provide insight into new potential therapeutic approaches.

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Section: Pathogen-induced Exacerbation Viralmentioning

confidence: 79%

Section: Pathogen-induced Exacerbation Viralmentioning

confidence: 79%

Section: Pathogen-induced Exacerbation Viralmentioning

confidence: 88%

Section: Bacterialmentioning

confidence: 98%

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Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation

et al. 2017

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“…In vivo. Experimental COPD and influenza infection were induced; miR-125a and -b were inhibited using specific antagomirs; and histopathology, IHC, immunoblotting, and cytometric bead array and data analyses were performed as previously described and/or as in Supplemental Methods (33,35,39,(59)(60)(61)(62)(63)(64)(65)(66)(67).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD

et al. 2017

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Integrated miRNA and mRNA expression profiling reveals dysregulated miRNA‐mRNA regulatory networks in eosinophilic and non‐eosinophilic chronic rhinosinusitis with nasal polyps

Wang

Luan

et al. 2021

Int Forum Allergy Rhinol

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Background: The precise mechanisms underlying pathogenesis of different subtypes of chronic rhinosinusitis with nasal polyps (CRSwNP) are still unclear.Emerging evidence indicates that microRNAs may play a role in the pathogenesis of CRSwNP. This study aimed to identify the dysregulated microRNA-messenger RNA (miRNA-mRNA) regulatory networks in eosinophilic (E) and noneosinophilic (non-E) CRSwNP. Methods: Whole-transcriptome sequencing was performed on nasal tissues of patients with ECRSwNP and non-ECRSwNP, and control subjects. An integrated analysis of miRNA and mRNA expression was conducted to identify key mRNAs and miRNAs involved in the pathogenesis of ECRSwNP and non-ECRSwNP. The miRNAs of interest and their target genes were validated using quantitative realtime polymerase chain reaction (PCR). Results: A group of differentially expressed mRNAs (DE-mRNAs) and miR-NAs (DE-miRs) were identified in ECRSwNP patients vs control subjects, non-ECRSwNP patients vs control subjects, and non-ECRSwNP vs ECRSwNP patients, respectively. Pathway enrichment analysis showed distinct immune and inflammatory functions associated with DE-mRNAs and target genes of DE-miRs in ECRSwNP vs control and non-ECRSwNP vs control groups. The miRNA-mRNA regulatory networks constructed with Cytoscape highlighted the roles of miR-154, miR-221, and miR-223 family miRNAs relating to both ECRSwNP and non-ECRSwNP, and the roles of the let-7 and miR-34/449 families in the development of non-ECRSwNP. Assessment using real-time PCR for the expression of miRNAs and target genes demonstrated highly consistent data with the RNA sequencing data. Conclusion: ECRSwNP and non-ECRSwNP patients express distinct miRNA-mRNA regulatory networks compared with control subjects, thus providing

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MicroRNA-21 drives severe, steroid-insensitive experimental asthma by amplifying phosphoinositide 3-kinase–mediated suppression of histone deacetylase 2

Abstract: 26Background: Severe, steroid-insensitive asthma is a substantial clinical problem accounting 27

Cited by 187 publications

References 84 publications

Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation

Mouse models of severe asthma: Understanding the mechanisms of steroid resistance, tissue remodelling and disease exacerbation

MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD

Integrated miRNA and mRNA expression profiling reveals dysregulated miRNA‐mRNA regulatory networks in eosinophilic and non‐eosinophilic chronic rhinosinusitis with nasal polyps

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