Evidence map›Paper›PMID 36936950›Full record

ArticleFrontiers in immunology2023

Skeletal myotube-derived extracellular vesicles enhance itaconate production and attenuate inflammatory responses of macrophages.

Atomu Yamaguchi, Noriaki Maeshige, Jiawei Yan, Xiaoqi Ma, Mikiko Uemura, Mami Matsuda, Yuya Nishimura, Tomohisa Hasunuma, Hiroyo Kondo, Hidemi Fujino and 1 more

Open access · goldFull text read
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Itaconate and its derivatives in human health and diseases.Signal transduction and targeted therapy · 2026
    Review
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  5. Article
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  7. MPPMolecular biology reports · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 3 countries.

Atomu YamaguchiDepartment of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Noriaki MaeshigeDepartment of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Jiawei YanSchool of Life Sciences and Technology, ShanghaiTech University, Shanghai, China.
Xiaoqi MaDepartment of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Mikiko UemuraDepartment of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Mami MatsudaGraduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan.
Yuya NishimuraGraduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan.
Tomohisa HasunumaGraduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan.
Hiroyo KondoDepartment of Food Science and Nutrition, Nagoya Women's University, Nagoya, Japan.
Hidemi FujinoDepartment of Rehabilitation Science, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Zhi-Min YuanDepartment of Environmental Health, Harvard University T.H Chan School of Public Health, Boston, MA, United States.
Kobe University · JPHarvard University · USNagoya Women's University · JPShanghaiTech University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Macrophages play an important role in the innate immunity. While macrophage inflammation is necessary for biological defense, it must be appropriately controlled. Extracellular vesicles (EVs) are small vesicles released from all types of cells and play a central role in intercellular communication. Skeletal muscle has been suggested to release anti-inflammatory factors, but the effect of myotube-derived EVs on macrophages is unknown. As an anti-inflammatory mechanism of macrophages, the immune responsive gene 1 (IRG1)-itaconate pathway is essential. In this study, we show that skeletal muscle-derived EVs suppress macrophage inflammatory responses, upregulating the IRG1-itaconate pathway. Methods: C2C12 myoblasts were differentiated into myotubes and EVs were extracted by ultracentrifugation. Skeletal myotube-derived EVs were administered to mouse bone marrow-derived macrophages, then lipopolysaccharide (LPS) stimulation was performed and inflammatory cytokine expression was measured by RT-qPCR. Metabolite abundance in macrophages after addition of EVs was measured by CE/MS, and IRG1 expression was measured by RT-PCR. Furthermore, RNA-seq analysis was performed on macrophages after EV treatment. Results: EVs attenuated the expression of LPS-induced pro-inflammatory factors in macrophages. Itaconate abundance and IRG1 expression were significantly increased in the EV-treated group. RNA-seq analysis revealed activation of the PI3K-Akt and JAK-STAT pathways in macrophages after EV treatment. The most abundant miRNA in myotube EVs was miR-206-3p, followed by miR-378a-3p, miR-30d-5p, and miR-21a-5p. Discussion: Skeletal myotube EVs are supposed to increase the production of itaconate

Indexed as

Extracellular VesiclesMicroRNAsAnimalsLipopolysaccharidesMacrophagesMiceMuscle Fibers, SkeletalPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSuccinatesitaconic acidLipopolysaccharidesMicroRNAsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSuccinatesextracellular vesicleIRG1itaconatemacrophageskeletal muscle

Identifiers

PMID36936950
PMCPMC10018131
OpenAlexW4322772127

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.