The DOI matches its Crossref record; 61 of the 62 references it cites were found in a registry or an index.
Muscle Releases Alpha-Sarcoglycan Positive Extracellular Vesicles Carrying miRNAs in the Bloodstream
Open accessAbstract
In the past few years, skeletal muscle has emerged as an important secretory organ producing soluble factors, called myokines, that exert either autocrine, paracrine or endocrine effects. Moreover, recent studies have shown that muscle releases microRNAs into the bloodstream in response to physical exercise. These microRNAs affect target cells, such as hormones and cytokines. The mechanisms underlying microRNA secretion are poorly characterized at present. Here, we investigated whether muscle tissue releases extracellular vesicles (EVs), which carry microRNAs in the bloodstream under physiological conditions such as physical exercise. Using density gradient separation of plasma from sedentary and physically fit young men we found EVs positive for TSG101 and alpha-sarcoglycan (SGCA), and enriched for miR-206. Cytometric analysis showed that the SGCA+ EVs account for 1-5% of the total and that 60-65% of these EVs were also positive for the exosomal marker CD81. Furthermore, the SGCA-immuno captured sub-population of EVs exhibited higher levels of the miR-206/miR16 ratio compared to total plasma EVs. Finally, a significant positive correlation was found between the aerobic fitness and muscle-specific miRNAs and EV miR-133b and -181a-5p were significantly up-regulated after acute exercise. Thus, our study proposes EVs as a novel means of muscle communication potentially involved in muscle remodeling and homeostasis.
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“These ELVs were also positive for CD81, TSG101 and miR-206”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Guescini et al., 2015
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“ELVs containing alpha-sarcoglycan (SGCA) a component of the dystrophin-glycoprotein complex involved in the stability of muscle fiber membranes, were found in human plasma”
From Skeletal Muscle-Released Extracellular Vesicles: State of the Art (2019) · cites this paper as Guescini et al., 2015
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Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · cited 1×
“After centrifugation at 18,000 g, protein concentration was determined by the Bradford assay [35].”
MethodAnalysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · cited 1×
“Quantification was performed according to the ΔCq method [34], miR-16 or the exogenously added spike-in cel-miR-39 were used as a reference.”
MethodValadi, H., Ekström, K., Bossios, A., Sjöstrand, M., Lee, J. J., & Lötvall, J. O. (2007) · Nature Cell Biology · doi:10.1038/ncb1596 · Cited by 12,834 · cited 1×
“Numerous studies indicate that circulating miRNAs may be protected from degradation by several complementary mechanisms, including their incorporation into secreted membrane vesicles such as microvesicles, exosomes or apoptotic bodies [16–18], or via the formation of RNA-binding protein complexes [19].”
Background(2014) · Medical Entomology and Zoology · Cited by 9,400
Skog, J., Würdinger, T., van Rijn, S., Meijer, D. H., Gainche, L., Curry, W. T., Carter, B. S., Krichevsky, A. M., & Breakefield, X. O. (2008) · Nature Cell Biology · doi:10.1038/ncb1800 · Cited by 5,001
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Arroyo, J. D., Chevillet, J. R., Kroh, E. M., Ruf, I. K., Pritchard, C. C., Gibson, D. F., Mitchell, P. S., Bennett, C. F., Pogosova-Agadjanyan, E. L., Stirewalt, D. L., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019055108 · Cited by 3,294 · cited 1×
“Numerous studies indicate that circulating miRNAs may be protected from degradation by several complementary mechanisms, including their incorporation into secreted membrane vesicles such as microvesicles, exosomes or apoptotic bodies [16–18], or via the formation of RNA-binding protein complexes [19].”
BackgroundMuscles, exercise and obesity: skeletal muscle as a secretory organ
Pedersen, B. K., & Febbraio, M. A. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.49 · Cited by 2,909 · cited 1×
“Therefore, the discovery that contracting muscle is a myokine-producing organ has opened up a whole new field of research on skeletal muscle [6].”
BackgroundMicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins
Vickers, K. C., Palmisano, B. T., Shoucri, B. M., Shamburek, R. D., & Remaley, A. T. (2011) · Nature Cell Biology · doi:10.1038/ncb2210 · Cited by 2,741 · cited 2×
“In the extracellular environment, miRNAs could be stabilized by EVs (such as exosomes, microvesicles or apoptotic bodies), HDL/LDLs, or protected by RNA-binding proteins (reviewed in [14,45]).”
BackgroundExosomes: Extracellular organelles important in intercellular communication
Mathivanan, S., Ji, H. L., & Simpson, R. J. (2010) · Journal of Proteomics · doi:10.1016/j.jprot.2010.06.006 · Cited by 2,581 · cited 1×
“11 g/mL, as previously described [37].”
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Items 201–227 of 227
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Iglesias‐Gutiérrez, E., Pinilla, L., Barbé, F., & de Gonzalo‐Calvo, D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822258-4.00007-9
Cardozo, C. P., & Gasperi, R. D. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.62205-5
Su, X., Huang, H., Liao, L., Xing, X., Ma, S., Xu, X., Tang, Q., Gao, X. Q., Yang, J., Li, M., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4158151
Qin, M., Xing, L., Wu, J., Wen, S., Luo, J., Sun, J., Chen, T., Fan, Y., Zhu, J., Yang, L., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-2041307/v1
Exercise-induced microRNA modulations and their role in cognition
Goldberg, M. (2022) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-9462
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Sharma, A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.10.540125
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Laube, W. (2023) · Springer eBooks · doi:10.1007/978-3-662-67753-7_14
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Laube, W. (2023) · Springer eBooks · doi:10.1007/978-3-662-67753-7_10
Simon, L., Bourgeois, B. L., Poret, J. M., & Molina, P. E. (2023) · Springer eBooks · doi:10.1007/978-3-031-32483-3_69
Tischer, D., Schranner, D., Kallabis, S., Braunsperger, A., Schönfelder, M., Gnad, T., Jost, P. J., Nesic, S., Renziehausen, F., Fester, L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.28.656129
“1f) , a potential marker of muscle-derived EVs (Guescini et al. 2015).”
Extracellular vesicles in clinical chemistry: A focus on biomarkers
Mas‐Bargues, C., Huete-Acevedo, J., Arnal-Forné, M., Atencia-Rabadán, S., & Borrás, C. (2025) · Advances in clinical chemistry · doi:10.1016/bs.acc.2025.06.001
Das, S. K., Deep, G., Comeau, M. E., & Langefeld, C. D. (2025) · International Journal of Obesity · doi:10.1038/s41366-025-01933-z
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Rusu, L., Aurora, U., Chivaran, A., Marin, M. I., Rusu, M. R., Spinu, A., Marin, M., Buciu, G., & Călina, M. L. (2025) · Bioengineering · doi:10.3390/bioengineering12121321
“Also, cell communication is affected by FWT due to the cytokines liberated during the FWT, and mediate gene expression in the target cells [27].”
Zhan, L., Zhang, J., Chen, Y., Chen, S., & Tai, X. (2026) · Clinical and Translational Discovery · doi:10.1002/ctd2.70122
Molecules in motion: A narrative review on exercise, exosomes and eating disorders.
Stoeren, M. S., Goleva-Fjellet, S., Edlund, K., & Bratland‐Sanda, S. (2026) · Complementary Therapies in Medicine · doi:10.1016/j.ctim.2026.103378
Etude et caractérisation des vésicules extracellulaires dans un contexte d’obésité
Amosse, J. (2019) · theses.fr (ABES) · doi:10.70675/2d90fa73z378bz47bdza83cz809db70f24fb
Secretion of neurotoxic vesicles by muscle cells of ALS patients
Gall, L. L. (2019) · theses.fr (ABES) · doi:10.70675/61e48a01z5133z45e6z8569z1b35b4b8fb4f
Engineering a skeletal muscle model to study extracellular vesicle dynamics
Fernández‐Rhodes, M., Rimington, R. P., Fleming, J. W., Capel, A. J., Davies, O. G., & Lewis, M. P. (2026) · Journal of Tissue Engineering · doi:10.1177/20417314261427541 · Cited by 1
“A study by Guescini et al. (2015) proposed α -SCGA as a potential marker of SM-derived EVs in plasma.”
InfluentialPinto, A. C., Ferreira, H. B., Barbosa, S., Sousa, T., Melo, T., Santos, L. L., Ferreira, R. M. S., Moreira‐Gonçalves, D., & Domingues, M. R. (2026) · Metabolomics · doi:10.1007/s11306-026-02445-1
“%) reach the bloodstream (Guescini et al., 2015 ; Watanabe et al., 2022 ).”
Ye, Q., Yuan, S., & Wang, D. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1849217
Extracellular vesicles as mediators of exercise effects in cancer
Aires, I., Moreira‐Gonçalves, D., D’Agostino, V. G., Ferreira, R. M., & Vitorino, R. M. P. (2026) · Molecular Medicine · doi:10.1186/s10020-026-01577-3
“…cells (CD105 ⁺ , CD146 ⁺ ), while skeletal muscle-derived EVs (SGCA ⁺ ) represent only approximately 5% of total circulating EVs, despite skeletal muscle comprising ~ 40% of body mass and being recognized as an endocrine organ (Guescini et al. 2015, Aatonen et al. 2014, Nederveen et al. 2021).”
Barkas, G. I., Daniil, Z. D., & Kotsiou, O. S. (2026) · Muscles · doi:10.3390/muscles5030055
“Skeletal muscle-derived EV populations have been associated with alpha-sarcoglycan (SGCA), muscle-enriched microRNAs such as miR-1, miR-133a/b, and miR-206, and proteins linked to contraction, energy metabolism, myogenesis, and proteostasis [21,40,41].”
Zhang, E., & Zhang, W. Z. (2026) · Journal of Biomedical Research · doi:10.7555/jbr.40.20260331
Małkowska, P., Sochacka, M., Proia, P., & Sawczuk, M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27198677
“Experimental evidence suggests that skeletal muscle-derived EVs are plausible contributors to exercise-induced inter-organ communication, and may participate in signaling toward distant organs, including the brain [54,55].”
Pinto, A. C., Corrales, F. J., Domingues, M. R., Ferreira, H. B., Moreira‐Gonçalves, D., Vitorino, R. M. P., Melo, T., & Ferreira, R. M. (2026) · Expert Review of Proteomics · doi:10.1080/14789450.2026.2750126
Metadata
- Authors
- Guescini, M., Canonico, B., Lucertini, F., Maggio, S., Annibalini, G., Barbieri, E., Luchetti, F., Papa, S., & Stocchi, V.
- Affiliations
- University of Urbino (IT)
- Corresponding author
- Guescini, Michele
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-05-08
- Volume
- 10
- Issue
- 5
- Pages
- e0125094
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4425492
- OpenAlex
- W219060072
- Cited by
- 228
- References
- 62
- Citations by year
- 2026: 19 · 2025: 31 · 2024: 26 · 2023: 27 · 2022: 33 · 2021: 24 · 2020: 22 · 2019: 18 · 2018: 11 · 2017: 11 · 2016: 5 · 2015: 1
- FWCI
- 4.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- CINECA IRIS Institutional Research information system (University of Urbino) (submittedVersion, cc-by)
- Funders
- Regione Marche
- Università degli Studi di Urbino Carlo Bo
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- extracellular vesicles, alpha-sarcoglycan, miR-206, microRNA secretion, myokines, skeletal muscle, physical activity, cardiorespiratory fitness, miR-133b, miR-181a-5p, TSG101, CD81, plasma vesicles, muscle remodeling, muscle homeostasis
- MeSH terms
- Extracellular Vesicles, Tsg101 Protein, Adult, Cell Communication, Centrifugation, Density Gradient, DNA-Binding Proteins, Gene Expression Regulation, Humans, Male, Transcription Factors, Signal Transduction, Exercise, Muscle, Skeletal, MicroRNAs, Sarcoglycans, Exosomes, Endosomal Sorting Complexes Required for Transport, Sedentary Behavior, Tetraspanin 28
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