Cited by 228Extracellular vesicles in diseaseExercise and Physiological ResponsesMuscle Physiology and Disorders

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 access

Guescini, Michele, Canonico, Barbara, Lucertini, Francesco, Maggio, Serena, Annibalini, Giosué, Barbieri, Elena, Luchetti, Francesca, Papa, Stefano, Stocchi, Vilberto·2015·PLoS ONE

DOI 10.1371/journal.pone.0125094PMC PMC4425492

Open this paper in CoChat — free account Open PDF

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0125094

Cites

61 of 61 references verified0 citation errors · 0 not checkable

Statistics

Fig 1 Density gradient separation of plasma EVs. Plasma EVs were purified using the serial ultracentrifugation protocol. The obtained pellet was then further separated using the Optiprep iodixanol density gradient. Fractions containing total EVs were identified by Western blot analysis with antibodies against Tsg101 (a) while EVs originating from muscle tissue were identified by the anti-SGCA (b). MiR-206 expression levels were quantified from each fraction using a specific TaqMan MicroRNA probe, expression levels were normalized versus the spike-in cel-miR-39 exogenously added and reported as fold change compared to the fraction 6 (c).CC BY · PubMed Central

Fig 2 Contour plot of plasma EVs. EVs were evaluated (P3) using size beads, identified by °(1 μm), *(2 μm) and (5.2 μm) (a). This gate strategy was performed to define the proper gate for events smaller than 1μm (P3), including MVs. Selected events are shown in contour plots (c) and (d), from samples labelled by goat anti-mouse (GaM) FITC (FL1-A) and anti-SGCA+ GaM FITC. P4 represents the area of FL1 positivity, drawn taking into account cluster distribution into the “negative” sample (MVs labelled with GaM only). Percentages are related to the following subpopulations: Purple: SGCA+ events; Blue: events less than 1 μm; Green: CD81+/SGCA+ events, shown in Fig 2A and 2B.CC BY · PubMed Central

Fig 3 Contour plots of size-selected EVs. Briefly, green clusters are those gated on the basis of their smaller size and SGCA positivity (previous contour plots: green cluster) and visualized for: a) for CD81 (FL4-A) and FSC localization; b) CD81 (FL4-A) and SGCA positivity (FL1-A), contour plot emphasizing co-expression of both markers.CC BY · PubMed Central

Fig 4 Isolation of alpha-sarcoglycan+ EVs from plasma using immunoaffinity capturing. Anti-alpha-sarcoglycan antibodies were conjugated to magnetic beads to isolate muscle EVs from plasma. Western blot analysis confirmed the presence of the exosomal marker Tsg101 in isolated EVs. Ponceau S Staining has been used as loading control (a). MicroRNA quantifications showed an increase in the miR-206/miR-16 ratio in the SGCA+ sub-population of EVs (SGCA-Beads) compared to total (total plasma EVs) or uncaptured EVs (Supernatant). MiR-206 expression levels were normalized versus the endogenous reference miR-16 and expressed as -ΔCq (where ΔCq = CqmiR-206-CqmiR-16) (b). Moreover, the quantification of miR-16 ratio in the SGCA+ sub-population of EVs compared to total or uncaptured EVs shows that SGCA-conjugated beads retained about 2–5% of the total amount of EVs, miR-16 expression levels were normalized versus the spike-in reference cel-miR-39 and expressed as -ΔCq (where ΔCq = CqmiR-16-Cqcel-miR-39) (c). Asterisks denote significant changes (p<0.05).CC BY · PubMed Central

Fig 5 Expression levels in specific EV miRNAs correlate with aerobic fitness. For each volunteer (n = 18), baseline miRNA levels from plasma EVs under resting condition were assigned to the corresponding aerobic fitness level estimated as VO2max. MiRNA expression levels were reported as -ΔCq (where ΔCq = CqmiR-206-CqmiR-16). A direct significant correlation (r = correlation coefficient) was observed between levels of miR-1, miR-133b, miR-206, miR-499 and miR-181a-5p (baseline) and VO2max. MiR-24 expression; which is stably expressed in blood, is the negative control.CC BY · PubMed Central

Fig 6 Modulation in circulating EV miRNAs in response to an aerobic exercise bout. The expression levels of miR-1, -133a, -133b, -146a, -181a-5p, -206, and -499 were evaluated in the circulating EVs of healthy volunteers (n = 7) at rest (Rest) and 1-hour after a 45-min aerobic exercise bout at 65% VO2max (Post-Exercise). MiRNA expression levels were reported as -ΔΔCt obtained subtracting the ΔCq at rest (where ΔCq = CqmiR-206-CqmiR-16) from the ΔCq Post-Exercise. MiR-24 is the negative control. Asterisks denote significant changes (p<0.05).CC BY · PubMed Central

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
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].”
Method
Analysis 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.”
Method
Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells
Valadi, 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
Untitled work
(2014) · Medical Entomology and Zoology · Cited by 9,400
Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers
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
Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma
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].”
Background
Muscles, 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].”
Background
MicroRNAs 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]).”
Background
Exosomes: 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].”

Show all 62 references

Sorted by citations

Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise
Whitham, M., Parker, B. L., Friedrichsen, M. H., Hingst, J. R., Hjorth, M., Hughes, W. E., Egan, C. L., Cron, L., Watt, K. I., Kuchel, R. P., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.001 · Cited by 700
Platelets, endothelial cells and leukocytes contribute to the exercise‐triggered release of extracellular vesicles into the circulation
Brahmer, A., Neuberger, E. W. I., Esch-Heisser, L., Haller, N., Jørgensen, M. M., Bæk, R., Möbius, W., Simon, P. D., & Krämer‐Albers, E. (2019) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2019.1615820 · Cited by 251
“exercise-related cell types such as muscle cells [alphasarcoglycan, [39], Figure 4(a)] or hepatocytes (asialoglycoprotein receptor, not shown) could not be detected.”
Background
Muscle-derived miR-34a increases with age in circulating extracellular vesicles and induces senescence of bone marrow stem cells
Fulzele, S., Mendhe, B., Khayrullin, A., Johnson, M. H., Kaiser, H., Liu, Y., Isales, C. M., & Hamrick, M. W. (2019) · Aging · doi:10.18632/aging.101874 · Cited by 220
Exercise-induced circulating extracellular vesicles protect against cardiac ischemia–reperfusion injury
Bei, Y., Xu, T., Lv, D., Yu, P., Xu, J., Che, L., Das, A., Tigges, J., Toxavidis, V., Ghiran, I. C., et al. (2017) · Basic Research in Cardiology · doi:10.1007/s00395-017-0628-z · Cited by 201
“In this regard, exercise-induced EVs derived from skeletal muscle deserve further investigation [1, 21, 40].”
Extracellular Vesicles and Exosomes: Insights From Exercise Science
Nederveen, J. P., Warnier, G., Carlo, A. D., Nilsson, M. I., & Tarnopolsky, M. A. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.604274 · Cited by 200
“…of anaerobic threshold (Sossdorf et al., 2010, 2011), ∼70% of VO2max (Lansford et al., 2016) and a single bout of high intensity interval exercise (Guiraud et al., 2013) all appear to increase PMVs. Work by Wilhelm et al. (2016) examined PMVs during a 1 h bout of heavy intensity exercise (∼65%…”
Background
Extracellular Vesicles in Blood: Sources, Effects, and Applications
Alberro, A., Iparraguirre, L., Fernandes, A., & Otaegui, D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158163 · Cited by 170
“In addition, the muscle tissue also secretes EVs and, indeed, striated muscle-specific miRNAs or myo-miRNAs have been found in human plasma EVs [75,76].”
Background
In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo
Yates, A. G., Pink, R. C., Erdbrügger, U., Siljander, P. R. M., Dellar, E. R., Pantazi, P., Akbar, N., Cooke, W. R., Vatish, M., Dias‐Neto, E., et al. (2022) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12151 · Cited by 187
“One of the most abundant miRNA in muscle-derived EVs is miR-206, which induces the development and differentiation of tissue, especially after muscle injury during exercise (Guescini et al., 2015).”
MicroRNAs as Important Regulators of Exercise Adaptation
da Silva, G. J. J., Bye, A., el Azzouzi, H., & Wisløff, U. (2017) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2017.06.003 · Cited by 158
Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice
Castaño, C., Mirasierra, M., Vallejo, M., Novials, A., & Párrizas, M. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016112117 · Cited by 156
“In particular, we observed up-regulation of miR-133a, miR-133b, and miR-206, three myomiRs whose circulating levels in vesicles have been shown by others to be increased in correlation with VO2 max in humans (41).”
Background
The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection
Burtscher, J., Millet, G. P., Place, N., Kayser, B., & Zanou, N. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126479 · Cited by 164
“Many of these molecules travel systemically (in blood or lymph) via extracellular vesicles that are today considered as key messengers of paracrine exercise signals [116–119], as they have been described to be released from skeletal muscle only in 2015 [120].”
Background
Muscle and Bone Health in Postmenopausal Women: Role of Protein and Vitamin D Supplementation Combined with Exercise Training
Agostini, D., Donati Zeppa, S., Lucertini, F., Annibalini, G., Gervasi, M., Ferri Marini, C., Piccoli, G., Stocchi, V., Barbieri, E., & Sestili, P. (2018) · Nutrients · doi:10.3390/nu10081103 · Cited by 151
“Furthermore, skeletal muscle expresses high levels of several microRNAs that can be delivered by exosomes [54].”
Background
The role of extracellular vesicles in skeletal muscle and systematic adaptation to exercise
Vechetti, I. J., Valentino, T., Mobley, C. B., & McCarthy, J. J. (2021) · The Journal of Physiology · doi:10.1113/jp278929 · Cited by 141
“These authors found that after an acute bout of endurance exercise there was a significant increase in the abundance of EV miR-181a-5p but no change in the abundance of miR-1, miR-133b, miR-206, miR-499 or miR-146a within EVs (Guescini et al. 2015).”
BackgroundInfluential
Skeletal Muscle-Released Extracellular Vesicles: State of the Art
Rome, S., Forterre, A., Mizgier, M. L., & Bouzakri, K. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00929 · Cited by 139
Circulating myomiRs: a new class of biomarkers to monitor skeletal muscle in physiology and medicine
Siracusa, J., Koulmann, N., & Banzet, S. (2017) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12227 · Cited by 135
“Whether exercise triggers the release of extracellular vesicles from muscle tissues is unclear in this study, because running exercise induced no changes in circulating myomiRs.(27)”
BackgroundMethodResultInfluential
Emerging role of extracellular vesicles in musculoskeletal diseases
Murphy, C., Withrow, J. S., Hunter, M., Liu, Y., Tang, Y., Fulzele, S., & Hamrick, M. W. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.09.006 · Cited by 123
“Not surprisingly, EVs released from skeletal muscle are enriched in these miRNAs, and circulating muscle-derived EVs transport these miRNAs [26].”
Background
Bone and Muscle Crosstalk in Aging
He, C., He, W., Hou, J., Chen, K., Huang, M., Yang, M., Luo, X., & Li, C. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.585644 · Cited by 129
MiR-124 contributes to M2 polarization of microglia and confers brain inflammatory protection via the C/EBP-α pathway in intracerebral hemorrhage
Yu, A., Zhang, T., Duan, H., Pan, Y., Zhang, X., Yang, G., Wang, J., Deng, Y., & Yang, Z. (2017) · Immunology Letters · doi:10.1016/j.imlet.2016.12.003 · Cited by 107
Extracellular Vesicles: Delivery Vehicles of Myokines
Trovato, E., Felice, V. D., & Barone, R. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00522 · Cited by 115
Effects of an acute bout of exercise on circulating extracellular vesicles: tissue-, sex-, and BMI-related differences
Rigamonti, A. E., Bollati, V., Pergoli, L., Iodice, S., Col, A. D., Tamini, S., Cicolini, S., Tringali, G., Micheli, R. D., Cella, S. G., et al. (2019) · International Journal of Obesity · doi:10.1038/s41366-019-0460-7 · Cited by 110
Effects of Acute Aerobic Exercise on Rats Serum Extracellular Vesicles Diameter, Concentration and Small RNAs Content
de Oliveira, G. P., Porto, W. F., Palu, C. C., Pereira, L. M., Petriz, B. A., de Almeida, J. A., Viana, J., Filho, N. N. A., Franco, O. L., & Pereira, R. W. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00532 · Cited by 108
“…vesicles include vesicles found in all ﬂuids investigated so far, such as urine (Gomes et al., 2014), saliva (Goodarzi et al., 2016), milk (Guescini et al., 2015), seminal (Gupta and Knowlton, 2007) and amniotic ﬂuids (Gutiérrez-Vázquez et al., 2013), serum (Hawley and Holloszy, 2009)…”
Circulating microRNAs in acute and chronic exercise: more than mere biomarkers
Sapp, R. M., Shill, D. D., Roth, S. M., & Hagberg, J. M. (2016) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00982.2016 · Cited by 109
“1 ↔ (9) Endurance running Healthy men ↔ ↔ ↔ ↔ ↔ (40) Half marathon Healthy, active men 1 1 1 (39) Marathon and 10 km run Healthy, trained men ↔ ↔ ↔ ↔ (25) Marathon Healthy, trained men 1 1 1 1 (8) Marathon Healthy, trained men 1 1 1 1 1 (75) Marathon Healthy, trained men 1 (20) Marathon Trained men and women with hype…”
Background
The mechanisms and treatments for sarcopenia: could exosomes be a perspective research strategy in the future?
Rong, S., Wang, L., Peng, Z., Liao, Y., Li, D., Yang, X., Nussler, A. K., Liu, L., Bao, W., & Yang, W. Q. (2020) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12536 · Cited by 110
“For instance, EVs-miR-133b and EVs-miR181a-5p were observed to be significantly up-regulated after exercise, which possibly may be related to muscle remodelling and homeostasis.(140) Recently, it has been discovered that muscle-derived EVs carrying senescence-associated miRNAs, such as miR-34a-5p (miR-34a), were able…”
Background
Biogenesis and function of extracellular vesicles in pathophysiological processes of skeletal muscle atrophy
Wang, W., Li, M., Chen, Z., Xu, L., Chang, M., Wang, K., Deng, C., Gu, Y., Zhou, S., Shen, Y., et al. (2022) · Biochemical Pharmacology · doi:10.1016/j.bcp.2022.114954 · Cited by 110
Exosomes and Extracellular RNA in Muscle and Bone Aging and Crosstalk
Qin, W., & Dallas, S. L. (2019) · Current Osteoporosis Reports · doi:10.1007/s11914-019-00537-7 · Cited by 99
Extracellular vesicle-shuttled miRNAs: a critical appraisal of their potential as nano-diagnostics and nano-therapeutics in type 2 diabetes mellitus and its cardiovascular complications
Prattichizzo, F., Matacchione, G., Giuliani, A., Sabbatinelli, J., Olivieri, F., de Candia, P., Nigris, V. D., & Ceriello, A. (2020) · Theranostics · doi:10.7150/thno.51605 · Cited by 99
“As expected, some of the EVs released during acute physical activity derive from the skeletal muscles, as evidenced by a large positivity for alpha-sarcoglycan [118], but also platelet, endothelial, and immune cells have been reported to contribute to the released EV pool [24].”
Background
Effects of exercise on exosome release and cargo in in vivo and ex vivo models: A systematic review
Estébanez, B., Jiménez‐Pavón, D., Huang, C., Cuevas, M. J., & González‐Gallego, J. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.30094 · Cited by 94
Sedentary and Trained Older Men Have Distinct Circulating Exosomal microRNA Profiles at Baseline and in Response to Acute Exercise
Nair, V. D., Ge, Y., Li, S., Pinças, H., Jain, N., Seenarine, N., Amper, M. A. S., Goodpaster, B. H., Walsh, M. J., Coen, P. M., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00605 · Cited by 92
Investigation of Circulating Extracellular Vesicle MicroRNA Following Two Consecutive Bouts of Muscle-Damaging Exercise
Lovett, J. A. C., Durcan, P., & Myburgh, K. H. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01149 · Cited by 85
“Both in vivo and in vitro studies have shown that miRs are selectively packaged into EVs (Forterre et al., 2014b; Guescini et al., 2015; GarciaContreras et al., 2017).”
Background
Acute resistance exercise modulates microRNA expression profiles: Combined tissue and circulatory targeted analyses
D’Souza, R. F., Markworth, J. F., Aasen, K. M. M., Zeng, N., Cameron‐Smith, D., & Mitchell, C. J. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181594 · Cited by 86
Bone marrow mesenchymal stem cell–derived exosomal miR‐206 promotes osteoblast proliferation and differentiation in osteoarthritis by reducing Elf3
Huang, Y., Zhang, X., Zhan, J., Yan, Z., Chen, D., Xue, X., & Pan, X. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16654 · Cited by 82
Skeletal muscle releases extracellular vesicles with distinct protein and microRNA signatures that function in the muscle microenvironment
Watanabe, S., Sudo, Y., Makino, T., Kimura, S., Tomita, K., Noguchi, M., Sakurai, H., Shimizu, M., Takahashi, Y., Sato, R., et al. (2022) · PNAS Nexus · doi:10.1093/pnasnexus/pgac173 · Cited by 81
“These results may be consistent with previous reports showing that SGCA-positive EVs constitute only 1% to 5% of total circulating EVs (46) and that most circulating exosomal miRNAs are derived from adipose tissue (47).”
BackgroundResult
microRNAs: Modulators of the underlying pathophysiology of sarcopenia?
Brown, D. M., & Goljanek‐Whysall, K. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.08.007 · Cited by 77
Muscle-derived small extracellular vesicles induce liver fibrosis during overtraining
Liu, Y., Zhou, R., Guo, Y., Hu, B., Xie, L., An, Y., Wen, J., Liu, Z., Zhou, M., Kuang, W., et al. (2025) · Cell Metabolism · doi:10.1016/j.cmet.2024.12.005 · Cited by 78
Denervation-related alterations and biological activity of miRNAs contained in exosomes released by skeletal muscle fibers
De Gasperi, R., Hamidi, S., Harlow, L. M., Ksiezak-Reding, H., Bauman, W. A., & Cardozo, C. P. (2017) · Scientific Reports · doi:10.1038/s41598-017-13105-9 · Cited by 75
Bone and muscle crosstalk in ageing and disease
Kirk, B., Lombardi, G., & Duque, G. (2025) · Nature Reviews Endocrinology · doi:10.1038/s41574-025-01088-x · Cited by 89
“In mice, 4–5% of circulating extracellular vesicles are muscle-derived (for example, tetraspanin + (such as CD9 + , CD63 + and CD81 + )) 150 , as they are in humans 151 (Fig.”
The impact of obesity on adipocyte-derived extracellular vesicles
Kwan, H. Y., Chen, M., Xu, K., & Chen, B. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03973-w · Cited by 78
The secretome of skeletal muscle cells: A systematic review
Florin, A., Lambert, C., Sanchez, C., Zappia, J., Durieux, N., Tieppo, A. M., Mobasheri, A., & Henrotin, Y. E. (2020) · Osteoarthritis and Cartilage Open · doi:10.1016/j.ocarto.2019.100019 · Cited by 73
Effects of Physical Exercise on the Expression of MicroRNAs: A Systematic Review
da Silva, F. C., Iop, R. D. R., Andrade, A., Costa, V. P., Filho, P. J. B. G., & da Silva, R. (2019) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003103 · Cited by 68
Blood flow-restricted resistance exercise alters the surface profile, miRNA cargo and functional impact of circulating extracellular vesicles
Just, J., Yan, Y., Farup, J., Sieljacks, P., Sloth, M., Venø, M. T., Gu, T., de Paoli, F. V., Nyengaard, J. R., Bæk, R., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-62456-3 · Cited by 65
Muscle and Systemic Molecular Responses to a Single Flywheel Based Iso-Inertial Training Session in Resistance-Trained Men
Annibalini, G., Contarelli, S., Lucertini, F., Guescini, M., Maggio, S., Ceccaroli, P., Gervasi, M., Marini, C. F., Fardetti, F., Grassi, E., et al. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00554 · Cited by 63
“Moreover, these results are consistent with those of recent studies demonstrating the potential relevance of exercise-derived EVs as markers of muscle function and exercise adaptation (Guescini et al., 2015; Whitham et al., 2018).”
BackgroundResultInfluential
Plasma-derived extracellular vesicles released after endurance exercise exert cardioprotective activity through the activation of antioxidant pathways
Lisi, V., Senesi, G., Bertola, N., Pecoraro, M., Bolis, S., Gualerzi, A., Picciolini, S., Raimondi, A., Fantini, C., Moretti, E., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102737 · Cited by 64
“Some of the miRNAs carried by circulating EVs obtained post-PE belong to the group of myomiRs, indicating the involvement of EVs in muscle regeneration processes following exercise [34].”
Background
The Protective Effect of Exercise in Neurodegenerative Diseases: The Potential Role of Extracellular Vesicles
Fuller, O. K., Whitham, M., Mathivanan, S., & Febbraio, M. A. (2020) · Cells · doi:10.3390/cells9102182 · Cited by 60
“A number of proteins have been observed in exercise-induced EVs, including CD36, flotillin-1, alpha-sarcoglycan, HSP72 and Aβ; however, the biological functions of these various proteins are currently unknown [192].”
Background
Extracellular vesicles released by oxidatively injured or intact C2C12 myotubes promote distinct responses converging toward myogenesis
Guescini, M., Maggio, S., Ceccaroli, P., Battistelli, M., Annibalini, G., Piccoli, G., Sestili, P., & Stocchi, V. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112488 · Cited by 59
“Our and other reports opened up the possibility that EVs convey signalling molecules allowing for intercellular regulation of gene expression [5,25,36].”
Result
Roles of Skeletal Muscle-Derived Exosomes in Organ Metabolic and Immunological Communication
Aoi, W., & Tanimura, Y. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.697204 · Cited by 57
“(31) reported that muscle-enriched miR-133b andmiR-181a-5p in EVs were elevated after acute exercise, and a positive correlation was found between aerobic fitness and circulating muscle-enriched miRNAs.”
Background
Plasma microRNA profiling distinguishes patients with frontotemporal dementia from healthy subjects
Grasso, M., Piscopo, P., Talarico, G., Ricci, L., Crestini, A., Tosto, G., Gasparini, M., Bruno, G., Denti, M. A., & Confaloni, A. (2019) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2019.01.024 · Cited by 54
Extracellular Vesicles as Communicators of Senescence in Musculoskeletal Aging
Alfonzo, M. C., Saedi, A. A., Fulzele, S., & Hamrick, M. W. (2022) · JBMR Plus · doi:10.1002/jbm4.10686 · Cited by 60
“EV secretion is increased with exercise,((20,21)) possibly through membrane (sarcolemma) damage that leads to calcium influx and exosome release.”
Background
Circulating exosome‐like vesicle and skeletal muscle microRNAs are altered with age and resistance training
Xhuti, D., Nilsson, M. I., Manta, K., Tarnopolsky, M. A., & Nederveen, J. P. (2023) · The Journal of Physiology · doi:10.1113/jp282663 · Cited by 63
“Herein, our findings confirm previous reports from Guescini et al. (2015) who observed the presence of TSG101 and muscle-specific miRNAs in α -SGCA + captured ELVs.”
BackgroundResult
Muscle-Derived Extracellular Vesicles Improved Disuse-Induced Osteoporosis by Rebalancing Bone Formation and Bone Resorption
Huang, H., Ma, S., Xing, X., Su, X., Xu, X., Tang, Q., Gao, X. Q., Yang, J., Li, M., Cheng, L., et al. (2022) · Acta Biomaterialia · doi:10.1016/j.actbio.2022.12.019 · Cited by 54
Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight
Doncheva, A. I., Romero, S., Ramírez‐Garrastacho, M., Lee-Ødegård, S., Kolnes, K. J., Tangen, D. S., Olsén, T., Drevon, C. A., Llorente, A., Dalen, K. T., et al. (2022) · Acta Physiologica · doi:10.1111/apha.13862 · Cited by 49
Circulating microRNA as Emerging Biomarkers of Exercise
Fernández‐Sanjurjo, M., de Gonzalo‐Calvo, D., Fernández‐Garcia, B., Díez‐Robles, S., Martínez-Canal, Á., Olmedillas, H., Dávalos, A., & Iglesias‐Gutiérrez, E. (2018) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000148 · Cited by 49
Exercise Training and Circulating Small Extracellular Vesicles: Appraisal of Methodological Approaches and Current Knowledge
Darragh, I. A. J., O’Driscoll, L., & Egan, B. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.738333 · Cited by 48
Extracellular vesicle microRNAs mediate skeletal muscle myogenesis and disease
Wang, H., & Wang, B. (2016) · Biomedical Reports · doi:10.3892/br.2016.725 · Cited by 44
“Guescini et al (66) investigated muscle tissue release of EVs carrying miRNAs in the bloodstream during physical exercise.”
Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling
Qin, M., Xing, L., Wu, J., Wen, S., Luo, J., Jiajie, S., Chen, T., Fan, Y., Zhu, J., Yang, L., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054561 · Cited by 44
“They can also enter the circulatory system, such as the blood, and may act on distant tissues [14,15].”
Background
Neuronal innervation regulates the secretion of neurotrophic myokines and exosomes from skeletal muscle
Huang, K., Upadhyay, G. K., Ahn, Y., Sakakura, M., Pagan‐Diaz, G. J., Cho, Y., Weiss, A. C., Huang, C., Mitchell, J. W., Li, J., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2313590121 · Cited by 42
“Several in vivo experiments reported that up to 5% of the exosomes in plasma were derived from skeletal muscle (53).”
Background
Modulation of the Circulating Extracellular Vesicles in Response to Different Exercise Regimens and Study of Their Inflammatory Effects
Maggio, S., Canonico, B., Ceccaroli, P., Polidori, E., Cioccoloni, A., Giacomelli, L., Marini, C. F., Annibalini, G., Gervasi, M., Benelli, P., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24033039 · Cited by 41
“For example, EV-miR-133 is upregulated following a single bout of moderate aerobic exercise [17] or after high-intensity interval exercise [34].”
BackgroundInfluential
Circulating miRNAs as Biomarkers of Acute Muscle Damage in Rats
Siracusa, J., Koulmann, N., Bourdon, S., Goriot, M., & Banzet, S. (2016) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.01.007 · Cited by 37
Skeletal Muscle Nrf2 Contributes to Exercise-Evoked Systemic Antioxidant Defense Via Extracellular Vesicular Communication
Gao, L., Wang, H., Tian, C., & Zucker, I. H. (2021) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000257 · Cited by 39
Resistance exercise differentially alters extracellular vesicle size and subpopulation characteristics in healthy men and women: an observational cohort study
Conkright, W. R., Beckner, M. E., Sterczala, A. J., Mi, Q., Lovalekar, M. T., Sahu, A., Krajewski, K. T., Martin, B. J., Flanagan, S. D., Greeves, J. P., et al. (2022) · Physiological Genomics · doi:10.1152/physiolgenomics.00171.2021 · Cited by 39
Emerging roles of extracellular vesicles in the intercellular communication for exercise-induced adaptations
Denham, J., & Spencer, S. J. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00215.2020 · Cited by 36
Signal Exchange through Extracellular Vesicles in Neuromuscular Junction Establishment and Maintenance: From Physiology to Pathology
Maggio, S., Ceccaroli, P., Polidori, E., Cioccoloni, A., Stocchi, V., & Guescini, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112804 · Cited by 34
“The findings that muscle cells release in vitro [83] and in vivo [84] exosomes containing miRNAs [84,85] are in agreement with the idea that EV-miRNAs can function as signaling molecules at the NMJ.”
Result
Extracellular vesicular miRNA expression is not a proxy for skeletal muscle miRNA expression in males and females following acute, moderate intensity exercise
Silver, J. L., Alexander, S. E., Dillon, H. T., Lamon, S., & Wadley, G. D. (2020) · Physiological Reports · doi:10.14814/phy2.14520 · Cited by 30
“Another normalization strategy used in previous human EV miRNA studies is to normalize to miR-16 (Guescini et al., 2015).”
BackgroundMethodResultInfluential
Epigenetics in the primary and secondary prevention of cardiovascular disease: influence of exercise and nutrition
Gevaert, A. B., Wood, N., Boen, J. R. A., Davos, C. H., Hansen, D., Hanssen, H., Krenning, G., Moholdt, T. T., Osto, E., Paneni, F., et al. (2022) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwac179 · Cited by 34
Non-coding RNAs in exercise immunology: A systematic review
Kotewitsch, M., Heimer, M., Schmitz, B., & Mooren, F. C. (2023) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2023.11.001 · Cited by 37
Muscle–bone interactions: movement in the field of mechano–humoral coupling of muscle and bone
Cardozo, C. P., & Graham, Z. (2017) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13411 · Cited by 32
Effects of an acute exercise bout in hypoxia on extracellular vesicle release in healthy and prediabetic subjects
Warnier, G., Groote, E. D., Britto, F. A., Delcorte, O., Nederveen, J. P., Nilsson, M. I., Pierreux, C. E., Tarnopolsky, M. A., & Deldicque, L. (2021) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00220.2021 · Cited by 32
Circulating microRNAs after a 24‐h ultramarathon run in relation to muscle damage markers in elite athletes
Chalchat, É., Charlot, K., García-Vicencio, S., Hertert, P., Baugé, S., Bourdon, S., Bompard, J., Farges, C., Martin, V., Bourrilhon, C., et al. (2021) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.14000 · Cited by 32
Expression levels of specific microRNAs are increased after exercise and are associated with cognitive improvement in Parkinson's disease
Silva, F. D., Rode, M. P., Vietta, G. G., Iop, R. D. R., Creczynski‐Pasa, T. B., Martin, A., & da Silva, R. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12257 · Cited by 32
Muscle-Derived Extracellular Vesicles Influence Motor Neuron Regeneration Accuracy
Madison, R. D., & Robinson, G. A. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.08.028 · Cited by 32
Non-coding RNAs and exercise: pathophysiological role and clinical application in the cardiovascular system
Gomes, C. P. C., de Gonzalo‐Calvo, D., Toro, R., Fernandes, T. M., Theisen, D., Wang, D., Devaux, Y., & on behalf of the Cardiolinc™ network (2018) · Clinical Science · doi:10.1042/cs20171463 · Cited by 31
Acute Exercise Increases Plasma Levels of Muscle-Derived Microvesicles Carrying Fatty Acid Transport Proteins
Nielsen, M. H., Sabaratnam, R., Pedersen, A. J. T., Højlund, K., & Handberg, A. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-02547 · Cited by 30
Extracellular Vesicles in Neurodegenerative Diseases: An Update
Sigdel, S., Swenson, S., & Wang, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713161 · Cited by 31
Extracellular vesicle transfer of miR-1 to adipose tissue modifies lipolytic pathways following resistance exercise
Burke, B. I., Ismaeel, A., Long, D. E., Depa, L. A., Coburn, P. T., Goh, J. Z., Saliu, T. P., Walton, B. J., Vechetti, I. J., Peck, B. D., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.182589 · Cited by 33
Detection and Isolation of Tissue‐Specific Extracellular Vesicles From the Blood
Newman, L. A., & Rowland, A. (2025) · Journal of Extracellular Biology · doi:10.1002/jex2.70059 · Cited by 28
“In healthy humans, for instance, one study suggested up to 20% may come from hepatocytes (Povero et al. 2020), 1%–5% from skeletal muscle (Guescini et al. 2015) and 1%–4% from the colon (Nazarova et al. 2021) and in pregnant women, up to 15% may arise from the placenta (Li et al. 2023).”
Yoga for heart failure: A review and future research
Pullen, P. R., Seffens, W. S., & Thompson, W. (2018) · International Journal of Yoga · doi:10.4103/ijoy.ijoy_24_17 · Cited by 28
“[34] Recently, circulating muscle‐specific miRNAs increased in blood samples obtained following prolonged aerobic exercise in humans,[35] and after stretching in animal models.”
Background
MiR-199-3p enhances muscle regeneration and ameliorates aged muscle and muscular dystrophy
Fukuoka, M., Fujita, H., Numao, K., Nakamura, Y., Shimizu, H., Sekiguchi, M., & Hohjoh, H. (2021) · Communications Biology · doi:10.1038/s42003-021-01952-2 · Cited by 30
Considerations for the Analysis of Small Extracellular Vesicles in Physical Exercise
Brahmer, A., Neuberger, E. W. I., Simon, P. D., & Krämer‐Albers, E. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.576150 · Cited by 28
“, 2018), dUC (Chaturvedi et al., 2015; Frühbeis et al., 2015; Guescini et al., 2015; Ma et al., 2018; Hou et al., 2019; Rigamonti et al., 2019), chemical precipitation (Bei et al.”
Background
Exercise, healthy ageing, and the potential role of small extracellular vesicles
McIlvenna, L. C., & Whitham, M. (2022) · The Journal of Physiology · doi:10.1113/jp282468 · Cited by 27
“It has been estimated that a total of ∼ 5% of the circulating sEV pool is derived from skeletal muscle (Estrada et al., 2022; Guescini et al., 2015).”
Background
The Combination of Physical Exercise with Muscle‐Directed Antioxidants to Counteract Sarcopenia: A Biomedical Rationale for Pleiotropic Treatment with Creatine and Coenzyme Q10
Guescini, M., Tiano, L., Genova, M. L., Polidori, E., Silvestri, S., Orlando, P., Fimognari, C., Calcabrini, C., Stocchi, V., & Sestili, P. (2017) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2017/7083049 · Cited by 32
“Muscle niche is regulated by growth and trophic factors, cytokines, and extracellular miRNAs carried by exosomes [62].”
Background
Circulating extracellular vesicle characteristics differ between men and women following 12 weeks of concurrent exercise training
Kargl, C. K., Sterczala, A. J., Santucci, D., Conkright, W. R., Krajewski, K. T., Martin, B. J., Greeves, J. P., O’Leary, T. J., Wardle, S. L., Sahu, A., et al. (2024) · Physiological Reports · doi:10.14814/phy2.16016 · Cited by 26
“…muscle-derived (SGCA + ), which is consistent with a growing number of studies (Annibalini et al., 2019; Brahmer et al., 2019; Estrada et al., 2021; Guescini et al., 2015; Ismaeel et al., 2023) demonstrating that only a small fraction of circulating EVs at rest or following exercise originate from…”
BackgroundInfluential
Non-coding RNAs as Putative Biomarkers of Cancer-Associated Cachexia
Donzelli, S., Farneti, A., Marucci, L., Ganci, F., Sacconi, A., Strano, S., Sanguineti, G., & Blandino, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00257 · Cited by 17
Single vesicle analysis reveals the release of tetraspanin positive extracellular vesicles into circulation with high intensity intermittent exercise
McIlvenna, L. C., Parker, H., Seabright, A. P., Sale, B., Anghileri, G., Weaver, S. R., Lucas, S. J. E., & Whitham, M. (2023) · The Journal of Physiology · doi:10.1113/jp284047 · Cited by 29
“…by experimental approaches that aimed to quantify changes, during exercise, in protein markers (Brahmer et al., 2019; Fruhbeis et al., 2015; Guescini et al., 2015; Helmig et al., 2015; Just et al., 2020) or microRNAs (D’souza et al., 2018; Guescini et al., 2015; Just et al., 2020; Lovett…”
Background
From sweat to hope: The role of exercise‐induced extracellular vesicles in cancer prevention and treatment
Llorente, A., Brokāne, A., Mlynska, A., Puurand, M., Sagini, K., Folkmane, S., Hjorth, M., Martín-Gracia, B., Romero, S., Skorinkina, D., et al. (2024) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12500 · Cited by 25
“Skeletal muscle indeed produces EVs that are enriched in muscle-specific proteins such as alpha-sarcoglycan (SGCA) (Guescini et al., 2015), ATP2A1, β -enolase, and desmin (Watanabe et al., 2022).”
BackgroundInfluential
Extracellular Vesicles as Players in the Anti-Inflammatory Inter-Cellular Crosstalk Induced by Exercise Training
Catitti, G., Bellis, D. D., Vespa, S., Simeone, P., Canonico, B., & Lanuti, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214098 · Cited by 26
The role of exercise parameters on small extracellular vesicles and microRNAs cargo in preventing neurodegenerative diseases
Fischetti, F., Poli, L., de Tommaso, M., Paolicelli, D., Greco, G., & Cataldi, S. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1241010 · Cited by 23
“, 2019); interestingly miRNA expression changes after exercise (Guescini et al., 2015; D’Souza et al., 2018).”
Background
Exercise improves cardiac fibrosis by stimulating the release of endothelial progenitor cell-derived exosomes and upregulating miR-126 expression
Fu, G., Wang, Z., & Hu, S. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1323329 · Cited by 24
Extracellular vesicles in cancer cachexia: deciphering pathogenic roles and exploring therapeutic horizons
Wang, Y., & Ding, S. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05266-9 · Cited by 25
“They are particularly interesting for their possible correlation with muscle remodeling and homeostasis [218].”
Background
Metabolic regulation of aging and age-related disease
Hamrick, M. W., & Stranahan, A. M. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101175 · Cited by 27
“In humans, exercise stimulates the release of EVs from skeletal muscle (Guescini et al., 2015; Whitham et al., 2018; Frühbeis et al., 2015).”
Background
Noncoding RNAs regulating cardiac muscle mass
Wadley, G. D., Lamon, S., Alexander, S. E., McMullen, J. R., & Bernardo, B. C. (2018) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00904.2018 · Cited by 23
“Exosomes released from skeletal muscle also contain many miRNA species that are implicated in cardiac hypertrophy, including miR-1, -133a/b, -222, and -208a (30, 52).”
Background
Functional Role of Extracellular Vesicles in Skeletal Muscle Physiology and Sarcopenia: The Importance of Physical Exercise and Nutrition
Lombardo, M., Aiello, G., Fratantonio, D., Karav, S., & Baldelli, S. (2024) · Nutrients · doi:10.3390/nu16183097 · Cited by 24
“A significant correlation was highlighted between aerobic capacity and plasma-isolated EVs (miRNA-133b and miRNA-181a-5p), which were found upregulated after acute PE [92]. miRNA-486-5p, miRNA-215-5p, and miRNA-941 levels were also found to be higher following regular PE.”
Background
The Role of Plasma Extracellular Vesicles in Remote Ischemic Conditioning and Exercise-Induced Ischemic Tolerance
Gu, T., Just, J., Stenz, K. T., Yan, Y., Sieljacks, P., Wang, J., Groennebaek, T., Jakobsgaard, J. E., Rindom, E., Herskind, J., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063334 · Cited by 22
“However, muscle-specific EVs have been described to swiftly increase during aerobic exercise and account for 1–5% of the total EV pool [29].”
Background
Advance in Drug Delivery for Ageing Skeletal Muscle
Li, Y., Chen, M., Zhao, Y., Li, M., Qin, Y., Cheng, S., Yang, Y., Yin, P., Zhang, L., & Tang, P. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.01016 · Cited by 22
“Guescini, M found similar results and further showed that muscle-specific miRNAs in EVs were significantly upregulated (Guescini et al., 2015).”
Result
Circulating Extracellular Vesicles: The Missing Link between Physical Exercise and Depression Management?
Soares, E. F. P., Reis, J., Rodrigues, M. F., Ribeiro, C., & Pereira, F. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22020542 · Cited by 22
“However, a FC analysis revealed that only 1–5% of total circulating EVs were SGCA+ [91].”
BackgroundMethodInfluential
The effect of the menstrual cycle on the circulating microRNA pool in human plasma: a pilot study
Lamon, S., Carré, J. L., Petito, G., Duong, H. P., Lüthi, F., Hiam, D., & Léger, B. (2022) · Human Reproduction · doi:10.1093/humrep/deac243 · Cited by 21
“A number of studies suggest highly selective and tightly regulated processes (Alexander et al. , 2015; Thomou et al. , 2017; Whitham et al. , 2018), which may underpin a whole level of cross-tissue communication (Guescini et al. , 2015; Whitham et al. , 2018).”
Influential
Extracellular Vesicles from Campylobacter jejuni CDT-Treated Caco-2 Cells Inhibit Proliferation of Tumour Intestinal Caco-2 Cells and Myeloid U937 Cells: Detailing the Global Cell Response for Potential Application in Anti-Tumour Strategies
Montanari, M., Guescini, M., Gundogdu, O., Luchetti, F., Lanuti, P., Ciacci, C., Burattini, S., Campana, R., Ortolani, C., Papa, S., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010487 · Cited by 20
Extracellular vesicle distribution and localization in skeletal muscle at rest and following disuse atrophy
Ismaeel, A., Pelt, D. W. V., Hettinger, Z. R., Fu, X., Richards, C. I., Butterfield, T. A., Petrocelli, J. J., Vechetti, I. J., Confides, A. L., Drummond, M. J., et al. (2023) · Skeletal Muscle · doi:10.1186/s13395-023-00315-1 · Cited by 23
“first reported that EVs positive for α-sarcoglycan, an integral membrane protein localized to the sarcolemma of skeletal muscle, could be detected in 1–5% of EVs found in the plasma [16].”
Background
Defining the influence of size‐exclusion chromatography fraction window and ultrafiltration column choice on extracellular vesicle recovery in a skeletal muscle model
Fernández‐Rhodes, M., Adlou, B., Williams, S., Lees, R., Peacock, B., Aubert, D., Jalal, A. R., Lewis, M. P., & Davies, O. G. (2023) · Journal of Extracellular Biology · doi:10.1002/jex2.85 · Cited by 22
“…have applied differential centrifugation (dUC) and density gradient centrifugation (Baci et al., 2020; Davies et al., 2021; Forterre et al., 2014; Guescini et al., 2010, 2015; Kim et al., 2018; Le Bihan et al., 2012; Romancino et al., 2013; Sork et al., 2018; Takafuji et al., 2020; Vumbaca et…”
BackgroundMethod
Emerging role of extracellular vesicles in the regulation of skeletal muscle adaptation
Vechetti, I. J. (2019) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00914.2018 · Cited by 21
Energetic Stress‐Induced Metabolic Regulation by Extracellular Vesicles
Crewe, C. (2023) · Comprehensive physiology · doi:10.1002/cphy.c230001 · Cited by 48
Men and women display distinct extracellular vesicle biomarker signatures in response to military operational stress
Conkright, W. R., Beckner, M. E., Sahu, A., Mi, Q., Clemens, Z. J., Lovalekar, M. T., Flanagan, S. D., Martin, B. J., Ferrarelli, F., Ambrosio, F., et al. (2022) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00664.2021 · Cited by 20
Extracellular Vesicles Released From Skeletal Muscle Post‐Chronic Contractile Activity Increase Mitochondrial Biogenesis in Recipient Myoblasts
Obi, P. O., Souza, T. F. G., Özerkliğ, B., Seif, S., Bydak, B., Klassen, N., Duhamel, T. A., West, A. R., Gordon, J. W., & Saleem, A. (2025) · Journal of Extracellular Vesicles · doi:10.1002/jev2.70045 · Cited by 22
“EVs in circulation largely originate from endothelial cells, platelets, erythrocytes, leukocytes, (Frühbeis et al. 2015, Brahmer et al. 2019), as well as skeletal muscle, albeit at very low levels ( ∼ 5% of total EVs) (Guescini et al. 2015).”
Influential

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: Guescini, Michele
Canonico, Barbara
Lucertini, Francesco
Maggio, Serena
Barbieri, Elena
Luchetti, Francesca
Papa, Stefano
Stocchi, Vilberto
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2015-05-08
Volume: 10
Issue: 5
Pages: e0125094
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0125094
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: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
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

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.

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 ›

Are you an author, or do you see a problem with this page? Request a review

Muscle Releases Alpha-Sarcoglycan Positive Extracellular Vesicles Carrying miRNAs in the Bloodstream

Abstract

Overview

Integrity signals

Figures

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks