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Cited by 139Extracellular vesicles in diseaseMuscle Physiology and DisordersCaveolin-1 and cellular processes

Skeletal Muscle-Released Extracellular Vesicles: State of the Art

Open access
Rome, Sophie, Forterre, Alexis, Mizgier, Maria Luisa, Bouzakri, Karim·2019·Frontiers in Physiology
DOI 10.3389/fphys.2019.00929PMC PMC6695556
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Abstract

All cells export part of their intracellular content into the extracellular space through the release of various types of extracellular vesicles (EVs). They are synthetized either from the budding of the plasma membrane [i.e., microparticles (MPs, 150-300 nm size)] or from the late endosomes in which intraluminal vesicles progressively (ILVs) accumulate during their maturation into multivesicular bodies (MVBs). ILVs are then released into the extracellular space through MVB fusion with the plasma membrane [i.e., exosomes (50-100 nm size)]. In the context of metabolic diseases, recent data have highlighted the role of EVs in inflammation associated with pancreas dysfunction, adipose tissue homeostasis, liver steatosis, inflammation, and skeletal muscle (SkM) insulin resistance (IR). Among these insulin-sensitive tissues, SkM is the largest organ in human and is responsible for whole-body glucose disposal and locomotion. Therefore, understanding the contribution of SkM-EVs in the development of diabetes/obesity/dystrophy/,-related diseases is a hot topic. In this review, we have summarized the role of SkM-EVs in muscle physiology and in the development of metabolic diseases and identify important gaps that have to be filled in order to have more precise information on SkM-EVs biological actions and to understand the functions of the different subpopulations of SkM-EVs on the whole-body homeostasis.

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Written from the paper’s full text.

TL;DR

This review summarizes the state of the art on skeletal muscle-released extracellular vesicles (SkM-EVs), covering their biogenesis, protein/lipid/RNA cargo, and reported roles in muscle physiology and metabolic disease. It concludes that SkM-EVs are promising paracrine/endocrine signals, but their systemic actions and clinical significance remain speculative.

Key findings

Skeletal muscle cells release heterogeneous EVs, including microparticles (MPs, 150–300 nm), exosomes/exosome-like vesicles (ELVs, 50–110 nm), and apoptotic bodies (300–2,000 nm); human myotube ELV-MT separated on iodixanol gradients yielded five potential subpopulations with distinct tetraspanin enrichments. Proteomic/RNA analyses identified 185 transcripts in ELVs and 4,431 in MPs from human SkM cells, and 59 proteins were commonly identified across three independent C2C12 ELV-MB proteomic analyses; ELV-MT were enriched in free-radical scavenging and cell-to-cell signaling proteins, while MPs were enriched in protein synthesis/folding/trafficking proteins. Functionally, ELV-MT treatment decreased myoblast proliferation and induced early differentiation markers (e.g., myogenin), and ELV-MT miRNAs were enriched for species targeting Sirt1; palmitate-induced insulin-resistant muscle ELVs transferred palmitate to recipient myotubes, up-regulating 240 genes including IL-6 and cyclin D1 and down-regulating Glut4 and differentiation markers. In mice, SkM-ELVs from diet-induced obese mice modulated 460 mRNAs in pancreatic MIN6B1 cells, and fluorescent SkM-ELVs labeled 9 organs after intraperitoneal injection; ELV-MT lipids were enriched in palmitic, stearic, oleic, palmitoleic, and lauric acid.

Methods

This is a narrative review, not a primary experimental study. It synthesizes published literature on EVs released from skeletal muscle cells, explants, and myofibers, including proteomic, lipidomic, and RNA-sequencing datasets from human and murine muscle models and mouse in vivo studies. The main analysis is a comparative, descriptive synthesis of SkM-EV biogenesis, cargo composition, and reported biological actions, with identification of gaps and future directions.

Limitations

Stated: the clinical significance of SkM-EV studies remains speculative until physiological models allow following EVs in blood vessels; all results suggesting information transfer between muscle and other tissues are based on in vitro data only, and it is not known whether SkM-ELVs reach the blood circulation and have systemic actions. Stated: purification methods have not been compared for muscle-released EVs and may select or enrich specific EV subpopulations; because no highly extensive vesicle purification was performed in published SkM-EV studies, the review uses the term exosome-like vesicles (ELV). Evident: as a narrative review, there is no systematic search or meta-analysis, and heterogeneity in isolation protocols and EV nomenclature across studies limits direct comparability.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3389/fphys.2019.00929

Cites

88 of 88 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 118 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    Gene enrichment analyses of proteins commonly identified in ELV-MT from human and murine SkM cells further confirmed that ELV-MT are enriched in proteins involved in exosome formation and intracellular trafficking.

    “Gene enrichment analyses of the proteins commonly identified in ELV-MT from human (Le Bihan et al., 2012) and murine (Forterre et al., 2014a) SkM cells further confirmed that ELV-MT are enriched in proteins involved in exosome formation and intracellular trafficking (e.g., endocytosis, vesicle fusion, and transport, and signaling pathways involved in vesicle cellular localization) (Figure 4B).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Le Bihan et al., 2012 source

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    • cites Forterre et al., 2014a

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  • Findingown data

    None of the GO categories previously found as significantly enriched in ELV proteins was identified in the 635 secreted proteins from C2C12 myoblasts.

    “None of the GO categories previously found as significantly enriched in ELV proteins (Figure 4B) was identified in the 635 secreted proteins.”
    Quote in the paperSubstantial claim
  • Findingown data

    The majority of proteins identified in ELV-MB was also found in ELV-MT.

    “Interestingly, the majority of the proteins identified in ELV-MB was also found in ELV-MT (Figure 5A).”
    Quote in the paperNot a substantial claim
  • Findingown data

    The C2C12 secretome was significantly enriched in the GO term cytokines.

    “By contrast, the C2C12 secretome was significantly enriched in GO term “cytokines.””
    Quote in the paperSubstantial claim
  • Premisecitation

    MPs were mainly cytosolic proteins, located in endoplasmic reticulum, Golgi vesicles, mitochondria, and cytoskeleton.

    “They were mainly cytosolic proteins, located in “endoplasmic reticulum,” “Golgi vesicles,” “mitochondria,” and “cytoskeleton.””
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    • cites Le Bihan et al., 2012 source

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  • Classified as probably not a substantial claim. 6
  • May combine two claims. 37

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Figure 5B shows the overlap between three independent proteomic analyses from C2C12 myoblasts, and 59 proteins were commonly identified.

    “Figure 5B shows the overlapping between three independent proteomic analyses from C2C12 myoblasts and the 59 proteins commonly identified are listed in Table 1.”
    Quote in the paperNot a substantial claim

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    Interpretationreasoning

    All these data suggest a high level of material exchange between different types of MVB-like structures, which could result in the release of a heterogeneous population of SkM-ELVs and may explain the diversity of their protein contents.

    “All these data suggest a high level of material exchange between different types of MVB-like structures, which could result in the release of a heterogeneous population of SkM-ELVs and may explain the diversity of their protein contents.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Muscle cells release extracellular vesicles into the extracellular milieu, which represent new paracrine and endocrine signals.

    “During the last decade, it has been shown that muscle cells also release extracellular vesicles (EVs) into the extracellular milieu, which represent new paracrine and endocrine signals that have modified our conceptual basis to explain how muscles communicate to other organs (Guescini et al., 2010; Le Bihan et al., 2012; Romancino et al., 2013; Forterre et al., 2014a).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Guescini et al., 2010 source

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    • cites Le Bihan et al., 2012 source

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    • cites Romancino et al., 2013 source

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    Premisecitation

    MPs were enriched in genes coding for proteins involved in protein synthesis, folding, and trafficking, RNA post-transcriptional modifications, translation modifications, and amino acid metabolism.

    “MPs were enriched in genes coding for proteins involved in “protein synthesis, folding, and trafficking,” “RNA post-transcriptional modifications,” “translation modifications,” and “amino acid metabolism.””
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Le Bihan et al., 2012 source

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    Premisecitation

    Myoblasts produce small exosome-like vesicles (ELV-MB), likely reflecting the intense macromolecule/RNA/lipid turnover that occurs during cell proliferation.

    “It has been described that myoblasts produce small ELVs (ELV-MB) (Guescini et al., 2010; Forterre et al., 2014a,b; Sork et al., 2018) likely reflecting the intense macromolecule/RNA/lipids turn-over that occurs during cell proliferation (Johnstone et al., 1991; Desdin-Mico and Mittelbrunn, 2017).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Guescini et al., 2010 source

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    • cites Forterre et al., 2014a,b

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    • cites Sork et al., 2018 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ELV-MB and ELV-MT may have different origins, and ELVs from myotubes would be produced mainly through budding of the plasma membrane.

    “Romancino et al. (2013) have suggested that ELV-MB and ELV-MT may have different origins and that ELVs from MT would be produced mainly through the budding of the plasma membrane.”
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    • cites Romancino et al., 2013 source

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    Interpretationcitation

    RNA/proteins of both nuclear and mitochondrial origins have been consistently identified in ELVs released from other cell types, suggesting that SkM may also release EVs originated from different MVB subpopulations.

    “it has to be noticed that RNA/proteins of both nuclear and mitochondrial origins have been consistently identified in ELVs released from other cell types suggesting that SkM may also release EVs originated from different MVB subpopulations (Vesiclepedia: http://microvesicles.org/index.html).”
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    • cites Vesiclepedia

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    Premisecitation

    The involvement of Alix for EV release seems to occur only in muscle cells, as knockdown of Alix did not affect the number of ELVs released from human liver stem-like cells.

    “Interestingly, the involvement of Alix for EV release seems to occur only in muscle cells as the knockdown of Alix did not affect the number of ELVs released from human liver stem-like cells (Iavello et al., 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Iavello et al., 2016 source

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    Interpretationreasoning

    These data indicated that SkM cells use distinct pathways for the release of distinct protein subsets with likely distinct biological actions.

    “These data indicated thus that SkM cell uses distinct pathways for the release of distinct protein subsets with likely distinct biological actions.”
    Quote in the paperSubstantial claim

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    Premisecitation

    MPs released from human myotubes were enriched in tetraspanin CD81 and in CLIC1 and galectin-1 (LGALS1) proteins and did not contain tetraspanins CD63, CD82, and CD9, which were found associated with ELVs from human myotubes.

    “MPs released from human MT were enriched in tetraspanin CD81 and in CLIC1 and galectin-1 (LGALS1) proteins and did not contain tetraspanins CD63, CD82, and CD9 which were found associated with ELVs from human MT (Figures 1D, 3; Le Bihan et al., 2012).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Le Bihan et al., 2012 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The endosomal system functions like a digital-analogue computer that regulates the specificity and robustness of the insulin signaling response in SkM.

    “For instance, the endosomal system functions like a digital-analogue computer that regulates the specificity and robustness of the insulin signaling response in the SkM (i.e., insulin induces translocation of key signaling proteins into endosome) (Balbis et al., 2000; Jethwa et al., 2015).”
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    • cites Balbis et al., 2000 source

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    Interpretationown data

    This result further supports the concept that protein sorting into ELVs appears to be selective and almost the same subset of proteins is exported whatever type of cell considered.

    “This result further supports the concept that proteins sorting into ELVs appears to be selective and almost the same subset of proteins is exported whatever type of cell considered.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    These data highlight two pathways for ELV release from muscle cells and suggest that the ratio between ELVs and MPs may vary between proliferation and differentiation.

    “Taken together, these data highlight two pathways for ELV release from muscle cells (i.e., for ELVs and MPs, respectively) and suggest that the ratio between ELVs and MPs may vary between proliferation and differentiation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Loss of Alix protein involved in ILV biogenesis in MVBs resulted in alteration of membrane budding, a decrease in the number of ELV released, and modifications of ELV-MT composition.

    “In their study, loss of Alix protein involved in ILV biogenesis in MVBs (Sun et al., 2015) resulted in alteration of membrane budding, a decrease in the number of ELV released and a modifications of ELV-MT composition”
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    • cites Romancino et al., 2013 source

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    Premisecitation

    Mitochondrial DNA, histones, and nuclear proteins were found in ELV-MB and ELV-MT.

    “Interestingly, mitochondrial DNA (Guescini et al., 2010), histones, and nuclear proteins were also found in ELV-MB (Guescini et al., 2010; Forterre et al., 2014a; Sork et al., 2018) and ELV-MT (Le Bihan et al., 2012; Forterre et al., 2014a).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Guescini et al., 2010 source

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    • cites Forterre et al., 2014a

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    • cites Sork et al., 2018 source

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    Interpretationcitation

    Only CD63 was commonly identified among all tetraspanins, likely reflecting protocol variabilities for SkM EV purifications.

    “Of note, only CD63 was commonly identified among all tetraspanins (Figure 3) likely reflecting the protocol variabilities for SkM EV purifications (Jeppesen et al., 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Jeppesen et al., 2019 source

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    Premisecitation

    For the majority of miRNAs, a good correlation was observed between miRNA levels in ELV-MB vs. myoblasts in two independent studies, and between ELVs released from myofibers vs. myofibers.

    “For the majority of miRNAs, a good correlation was observed between miRNA levels in ELV-MB vs. MB in two independent studies (Forterre et al., 2014b; Sork et al., 2018), and between ELVs released from myofibers vs. myofibers (De Gasperi et al., 2017)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Forterre et al., 2014b

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    • cites Sork et al., 2018 source

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    • cites De Gasperi et al., 2017 source

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    Premisecitation

    Both ELV-MT protein and miRNA contents were transferred into proliferating myoblasts.

    “Indeed, it was shown that both ELV-MT protein and miRNA contents were transferred into proliferating myoblasts (Forterre et al., 2014a,b).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Forterre et al., 2014a,b

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    Premisecitation

    C2C12 ELV-MB also contained tRNAs and Y RNA (mainly RNY1).

    “C2C12 ELV-MB also contained tRNAs (Sork et al., 2018) and Y RNA (mainly RNY1) (Forterre et al., 2014b; Sork et al., 2018).”
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    • cites Sork et al., 2018 source

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    • cites Forterre et al., 2014b

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    Premisecitation

    miR-720 was enriched in myofiber-derived ELVs compared with parent myofibers, and inversely for miR-1.

    “Similarly, miR-720 was enriched in myofiber-derived ELVs compared with parent myofibers and inversely for miR-1 (De Gasperi et al., 2017).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites De Gasperi et al., 2017 source

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  • May combine two claims.

    Interpretationcitation

    The abundance of the 185 ELV mRNAs correlated with their abundance in myotubes, indicating that myotubes release a specific subset of transcripts in ELVs, and not only the most concentrated one.

    “The abundance of the 185 ELV mRNAs correlated with their abundance in myotubes, indicating that myotubes release a specific subset of transcripts in ELVs, and not only the most concentrated one.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Le Bihan et al., 2012 source

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  • May combine two claims.

    Interpretationnone given

    SkM-released EVs have important paracrine actions that would participate in muscle physiology and may have an impact at whole-body homeostasis.

    “In that context, it has been found that SkM-released EVs have important paracrine actions that would participate in muscle physiology and may have an impact at the whole-body homeostasis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Treatment of myoblasts with ELV-MT but not ELV-MB resulted in a decrease in myoblast proliferation and in the induction of early markers of differentiation (e.g., myogenin mRNA).

    “Treatment of myoblasts with ELV-MT but not ELV-MB resulted in a decrease in myoblast proliferation and in the induction of early markers of differentiation (e.g., myogenin mRNA) (Forterre et al., 2014a).”
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    • cites Forterre et al., 2014a

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    Interpretationcitation

    ELVs in mammalian serum might have unsuspected functions during embryogenesis and in the regulation of cellular adaptations that lead to muscle hypertrophy, hyperplasia, and metaplasia.

    “this result also suggests that ELVs in mammalian serum might have unsuspected functions during embryogenesis and in the regulation of cellular adaptations that lead to muscle hypertrophy, hyperplasia, and metaplasia.”
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    • cites Aswad et al., 2016 source

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    Premisecitation

    Removing ELVs from bovine serum of cell culture affected C2C12 proliferation (decrease of Cyclin D1 and Sirt1 mRNA levels) and committed cells to differentiate prematurely (induction of myogenin mRNA before myoblast fusion).

    “Furthermore, it was found that removing ELVs from bovine serum of cell culture, affected C2C12 proliferation (i.e., decrease of Cyclin D1 and Sirt1 mRNA levels) and committed cells to differentiate prematurely (induction of myogenin mRNA before myoblast fusion) (Aswad et al., 2016).”
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    • cites Aswad et al., 2016 source

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    Premisecitation

    Only the small RNA population has been further analyzed and was found highly enriched in piRNAs and miRNAs.

    “Only the small RNA population has been further analyzed (Forterre et al., 2014b; Sork et al., 2018; Xu et al., 2018), and was found highly enriched in piRNAs and miRNAs (Figure 6B; Sork et al., 2018).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Forterre et al., 2014b

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    • cites Xu et al., 2018

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    Premisecitation

    Cartonectin is a new cytokine, a paralog of adiponectin, contained as a transmembrane protein in adipocyte-released EVs and in EVs isolated from serum.

    “Cartonectin is a new cytokine, paralog of adiponectin contained as a transmembrane protein in adipocyte-released EVs and in EVs isolated from serum (Phoonsawat et al., 2014).”
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    • cites Phoonsawat et al., 2014 source

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    Premisecitation

    All studies reported that individual miRNAs deviate from the relationship: some miRNAs expressed in muscle cells were not detected in ELV-MB and/or ELV-MT; others were found at a higher rate in ELV-MB vs. myoblasts.

    “Interestingly, all studies reported also that individual miRNAs deviate from this relationship, i.e., some miRNAs expressed in muscle cells were not detected in ELV-MB (Forterre et al., 2014b) and/or ELV-MT (Figure 6D; Forterre et al., 2014b); other were found at higher rate in ELV-MB vs. myoblasts [miR-451, miR-6239, miR-6,240, miR-6236, miR-144, miR-223, miR-5112, miR-3062, miR-142a, and miR-213”
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    Premisecitation

    A single bout of exhaustive exercise triggers the release of EVs with the size and marker profile of exosomes, which are cleared from the circulation during the early recovery period after cycling, but stay elevated after running exercise.

    “a single bout of exhaustive exercise triggers the release of EVs with the size and marker profile of exosomes, which are cleared from the circulation during the early recovery period after cycling, but stay elevated after running exercise.”
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    • cites Frühbeis et al., 2015 source

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    Premisecitation

    Twenty-four hours after injection of fluorescent ELVs in the right tibialis anterior, fluorescence is detected in the left TA and in the right quadriceps.

    “Twenty-four hours after injection, fluorescence was detected in the left TA and in the right quadriceps too”
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    • cites Jalabert et al., 2016 source

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    Premisecitation

    IL-6 and cyclin D1 are strongly upregulated, whereas Glut4 is downregulated, in recipient myotubes after transfer of palmitate contained in ELV-MT from DIO mice.

    “the pro-inflammatory cytokine IL-6 and the cell cycle regulator cyclin D1 were strongly upregulated, whereas Glut4 involved in glucose uptake was downregulated.”
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    • cites Aswad et al., 2014 source

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    Premisecitation

    Statins target chemokines to MVBs in endothelial cells.

    “statins, used to reduce cholesterol level in patients and to prevent cardiovascular diseases target chemokines to MVBs in endothelial cells”
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    • cites Hol et al., 2012 source

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    Premisecitation

    Myoblasts incubated with ELVs released from myotubes pre-treated with H2O2 leads to a reduction in myotube diameter and to a stimulation of myoblast proliferation.

    “myoblasts incubated with ELVs released from myotubes pre-treated with H2O2 that mimics an oxidative stress, leads to a reduction in myotube diameter and to a stimulation of myoblast proliferation”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Guescini et al., 2017 source

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    Premisecitation

    SkM-ELVs mediate the transfer of miRNAs from insulin-resistant muscles into MIN6B1 and affect the expression of proliferative genes such as Ptch1.

    “Additional bioinformatic analyses combined with in vitro experiments demonstrated that SkM-ELVs mediated the transfer of miRNAs from insulin-resistant muscles into MIN6B1 and affected the expression of proliferative genes such as Ptch1”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Jalabert et al., 2016 source

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    Premisecitation

    Expressions of 460 mRNAs are significantly modulated, including genes involved in immune responses known to be affected in pancreatic islets of diabetic patients.

    “Microarray data analyses showed that the expressions of 460 mRNAs were significantly modulated including genes involved in immune responses known to be affected in pancreatic islets of diabetic patients”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Esser et al., 2014 source

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  • May combine two claims.

    Premisecitation

    Treatment of C2C12 myotubes with dexamethasone for 48 h reduces intracellular miR-23a and increases its ELV-MT abundance.

    “treatment of C2C12 myotubes with dexamethasone for 48 h reduced the intracellular level of miR-23a but increased its ELV-MT abundance.”
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    • cites Hudson et al., 2014 source

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  • May combine two claims.

    Premisecitation

    Palmitate contained in ELV-MT from DIO mice is transferred in recipient myotubes and results in up-regulation of 240 genes involved in cell cycle and cellular adhesion.

    “palmitate contained in ELV-MT from DIO mice was transferred in recipient myotubes and resulted in the up-regulation of 240 genes involved in cell cycle and cellular adhesion.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Aswad et al., 2014 source

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  • May combine two claims.

    Premisecitation

    These ELVs are positive for CD81, TSG101 and miR-206.

    “These ELVs were also positive for CD81, TSG101 and miR-206”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Guescini et al., 2015 source

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    Premisecitation

    After denervation, muscle fibers release a new population of ELVs enriched in miR-206 able to downregulate Smarcd1 and Runx2 proteins in NIH3T3 adipocytes.

    “after denervation, muscle fiber released a new population of ELVs enriched in miR-206 able to downregulate the expression of Smarcd1 and Runx2 proteins into NIH3T3 adipocytes”
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    • cites De Gasperi et al., 2017 source

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39 of 39

  • The paper relies on this without support.

    Skeletal muscle is the largest organ in the human body and is responsible for whole-body glucose disposal, energy homeostasis, locomotion, and serves as a body protein pool.

    “Among these insulin-sensitive tissues, SkM is the largest organ in human and is responsible for whole-body glucose disposal and locomotion.”
    “Skeletal muscle (SkM) is the largest organ in the human body. It is responsible for whole-body glucose and energy homeostasis, locomotion, and serves as body protein pool.”

  • The paper relies on this without support.

    The different EV isolation methods have not been compared for muscle-released EVs and may result in the selection or enrichment of specific EV subpopulations.

    “It has to be noticed, however, that these different methods have not been compared for muscle-released EVs and may result in the selection or enrichment of specific EV subpopulations.”

  • The paper relies on this without support.

    No highly extensive vesicle purification was performed in published studies working on isolated EVs from SkM cells, SkM explants, or myofibers.

    “because no highly extensive vesicle purification was performed in published studies working on isolated EVs from SkM cells, SkM explants, or myofibers”

  • The paper relies on this without support.

    The contribution of ELVs and MPs in muscle physiology has never been fully characterized, and their specific biological functions on recipient cells are not known.

    “The contribution of these two types of vesicles in muscle physiology has never been fully characterized, and their specific biological functions on recipient cells are not known.”

  • The paper relies on this without support.

    SkM-ELVs have no effect on insulin secretion.

    “Because SkM-ELVs have no effect on insulin secretion”
5 of 5

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Each contradiction between two passages listed here was confirmed by an independent check.

  • Exosome size ranges differ

    Minor

    The abstract gives an exosome size range ending at 100 nm, while the introduction gives one ending at 110 nm.

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Authors
Rome, S., Forterre, A., Mizgier, M. L., & Bouzakri, K.
Affiliations
  • Inserm (FR)
  • Institut Méditerranéen d’Océanologie (FR)
Corresponding author
Rome, Sophie
ORCID
Venue
Frontiers in Physiology
Publisher
Frontiers Media SA
Published
2019-08-09
Volume
10
Pages
929-929
ISSN
1664-042X (ISSN-L)
DOI
10.3389/fphys.2019.00929
PMC
PMC6695556
OpenAlex
W2958833020
Semantic Scholar
454de326714d1b4e2f1a93d5610b8fb52a4a65f7
Cited by
139
References
88
Citations by year
2026: 13 · 2025: 14 · 2024: 21 · 2023: 24 · 2022: 26 · 2021: 23 · 2020: 16 · 2019: 2
FWCI
1.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
European Commission (HORIZON2020, 753670)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Keywords
skeletal muscle, extracellular vesicles, exosomes, microparticles, insulin resistance, metabolic disorders, diabetes mellitus, obesity, muscular dystrophy, inflammation, adipose tissue homeostasis, hepatic steatosis, glucose homeostasis, multivesicular bodies, intraluminal vesicles

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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