MicroRNA-451a in extracellular, blood-resident vesicles attenuates macrophage and dendritic cell responses to influenza whole-virus vaccine

Okamoto, Masaaki; Fukushima, Yoshio; Kouwaki, Takahisa; Daito, Takuji; Kohara, Michinori; Kida, Hiroshi; Oshiumi, Hiroyuki

doi:10.1074/jbc.ra118.003862

Cited by 36 publications

(50 citation statements)

References 64 publications

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“…Till date, several researches have demonstrated that miR-451a could inhibit the proliferation and differentiation of benign and malignant tumour cell and also affect the chemosensitivity of the tumour cells. Moreover, miR-451a in extracellular vesicles has been reported to influence the functions of immune cells, such as macrophages and dendritic cells [28,[33][34][35][36]. Hence, in the present study the predominantly enriched miR-451a in exosomes may be speculated to act as an important mediator in TRIM.…”

Section: Discussionmentioning

confidence: 48%

MicroRNA Profiling of Exosomes Derived from Red Blood Cell Units: Implications in Transfusion-Related Immunomodulation

Huang

Zhu

Fan

et al. 2019

BioMed Research International

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Purpose. To elucidate the microRNAs existent in exosomes derived from stored red blood cell (RBC) unit and their potential function. Materials and Methods. Exosomes were isolated from the supernatant derived from stored RBC units by sequential centrifugation. Isolated exosomes were characterized by TEM (transmission electron microscopy), western blotting, and DLS (dynamic light scattering). MicroRNA (miRNA) microarray was performed to detect the expression of miRNAs in 3 exosome samples. Results revealed miRNAs that were simultaneously expressed in the 3 exosome samples and were previously reported to exist in mature RBCs. Functions and potential pathways of some detected miRNAs were illustrated by bioinformatic analysis. Validation of the top 3 abundant miRNAs was carried out by qRT-PCR (quantitative reverse transcription‐polymerase chain reaction). Results. TEM and DLS revealed the mean size of the exosomes (RBC-derived) as 64.08 nm. These exosomes exhibited higher abundance of short RNA than the long RNA. 78 miRNAs were simultaneously detected in 3 exosome samples and mature RBCs. Several biological processes might be impacted by these miRNAs, through their target gene(s) enriched in a particular signalling pathway. The top 3 (abundant) miRNAs detected were as follows: miR-125b-5p, miR-4454, and miR-451a. qRT-PCR revealed higher abundance of miR-451a than others. Only miR-4454 and miR-451a abundance tended to increase with increasing storage time. Conclusion. Exosomes derived from stored RBC units possessed multiple miRNAs and, hence, could serve various functions. The function of exosomes (RBC-derived) might be implemented partly by the predominantly enriched miR-451a.

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Section: Discussionmentioning

confidence: 48%

MicroRNA Profiling of Exosomes Derived from Red Blood Cell Units: Implications in Transfusion-Related Immunomodulation

Huang

Zhu

Fan

et al. 2019

BioMed Research International

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“…Intriguingly, miR-195 has been implied in the pathophysiology of heart failure [39] and could play a role in the (dys)regulation of adrenergic-mediated responses, known to be critical in failing heart where they regulate both fibrosis and inflammation [40][41][42][43][44][45][46]: for instance, miR-195 has been reported to be upregulated by isoproterenol in the heart during catecholamine-induced hypertrophy [47]. Moreover, our findings pave the way for future investigation on the potential role of cardiosomal miRNAs in long-distance communications, since extracellular vesicles enriched in miRNAs have been recently found in blood [48,49]. Indeed, cells need to communicate efficiently with each other in order to propagate signals and coordinate functions [22].…”

Section: Discussionmentioning

confidence: 54%

Cardiosomal microRNAs Are Essential in Post-Infarction Myofibroblast Phenoconversion

Morelli

Shu

Sardu

et al. 2019

IJMS

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The inclusion of microRNAs (miRNAs) in extracellular microvesicles/exosomes (named cardiosomes when deriving from cardiomyocytes) allows their active transportation and ensures cell-cell communication. We hypothesize that cardiosomal miRNAs play a pivotal role in the activation of myofibroblasts following ischemic injury. Using a murine model of myocardial infarction (MI), we tested our hypothesis by measuring in isolated fibroblasts and cardiosomes the expression levels of a set of miRNAs, which are upregulated in cardiomyocytes post-MI and involved in myofibroblast phenoconversion. We found that miR-195 was significantly upregulated in cardiosomes and in fibroblasts isolated after MI compared with SHAM conditions. Moreover, primary isolated cardiac fibroblasts were activated both when incubated with cardiosomes isolated from ischemic cardiomyocytes and when cultured in conditioned medium of post-MI cardiomyocytes, whereas no significant effect was observed following incubation with cardiosomes or medium from sham cardiomyocytes. Taken together, our findings indicate for the first time that a cardiomyocyte-specific miRNA, transferred to fibroblasts in form of exosomal cargo, is crucial in the activation of myofibroblasts.

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“…Targeting EV production can therefore be a potential strategy of improving MRC-5 cell-based rabies vaccine production. Additionally, miRNAs in EVs affect the response to the influenza whole-virus vaccine (WV) (Okamoto et al, 2018). miR-451a is abundant in human serum EVs and its presence in blood-circulating EVs can attenuate the innate immune response of macrophages and dendritic cells to the inactivated influenza WV.…”

Section: Evs As a Negative Factor In Vaccine Productionmentioning

confidence: 99%

Cloaked Viruses and Viral Factors in Cutting Edge Exosome-Based Therapies

Dogrammatzis

Waisner

Kalamvoki

2020

Front. Cell Dev. Biol.

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Extracellular vesicles (EVs) constitute a heterogeneous group of vesicles released by all types of cells that play a major role in intercellular communication. The field of EVs started gaining attention since it was realized that these vesicles are not waste bags, but they carry specific cargo and they communicate specific messages to recipient cells. EVs can deliver different types of RNAs, proteins, and lipids from donor to recipient cells and they can influence recipient cell functions, despite their limited capacity for cargo. EVs have been compared to viruses because of their size, cell entry pathways, and biogenesis and to viral vectors because they can be loaded with desired cargo, modified, and re-targeted. These properties along with the fact that EVs are stable in body fluids, they can be produced and purified in large quantities, they can cross the blood-brain barrier, and autologous EVs do not appear to cause major adverse effects, have rendered them attractive for therapeutic use. Here, we discuss the potential for therapeutic use of EVs derived from virus infected cells or EVs carrying viral factors. We have focused on six major concepts: (i) the role of EVs in virus-based oncolytic therapy or virus-based gene delivery approaches; (ii) the potential use of EVs for developing viral vaccines or optimizing already existing vaccines; (iii) the role of EVs in delivering RNAs and proteins in the context of viral infections and modulating the microenvironment of infection; (iv) how to take advantage of viral features to design effective means of EV targeting, uptake, and cargo packaging; (v) the potential of EVs in antiviral drug delivery; and (vi) identification of novel antiviral targets based on EV biogenesis factors hijacked by viruses for assembly and egress. It has been less than a decade since more attention was given to EV research and some interesting concepts have already been developed. In the coming years, additional information on EV biogenesis, how they are hijacked and utilized by pathogens, and their impact on the microenvironment of infection is expected to indicate avenues to optimize existing therapeutic tools and develop novel approaches.

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MicroRNA-451a in extracellular, blood-resident vesicles attenuates macrophage and dendritic cell responses to influenza whole-virus vaccine

Abstract: The authors declare that they have no conflicts of interest with the contents of this article. This article contains Figs. S1-S6 and Table S1. The microarray data were deposited to the Gene Expression Omnibus (GEO) database under GEO accession number GSE100128.

Cited by 36 publications

References 64 publications

MicroRNA Profiling of Exosomes Derived from Red Blood Cell Units: Implications in Transfusion-Related Immunomodulation

MicroRNA Profiling of Exosomes Derived from Red Blood Cell Units: Implications in Transfusion-Related Immunomodulation

Cardiosomal microRNAs Are Essential in Post-Infarction Myofibroblast Phenoconversion

Cloaked Viruses and Viral Factors in Cutting Edge Exosome-Based Therapies

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