title: Muscle Releases Alpha-Sarcoglycan Positive Extracellular Vesicles Carrying miRNAs in the Bloodstream.
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.
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Guescini
authors.affiliation: Department of Human, Environment and Nature Science, University of Urbino Carlo Bo, Urbino, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Canonico
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lucertini
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Maggio
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
authors.forename: Giosué
authors.initials: G
authors.lastname: Annibalini
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Barbieri
authors.affiliation: Department of Human, Environment and Nature Science, University of Urbino Carlo Bo, Urbino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Luchetti
authors.affiliation: Department of Human, Environment and Nature Science, University of Urbino Carlo Bo, Urbino, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Papa
authors.affiliation: Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, Italy.
authors.forename: Vilberto
authors.initials: V
authors.lastname: Stocchi
mesh_terms: D000328:Adult; D002450:Cell Communication; D002499:Centrifugation, Density Gradient; D004268:DNA-Binding Proteins / Q000097:blood / Q000235:genetics; D056827:Endosomal Sorting Complexes Required for Transport / Q000097:blood / Q000235:genetics; D015444:Exercise; D055354:Exosomes / Q000737:chemistry / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000737:chemistry* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D049031:Sarcoglycans / Q000097:blood* / Q000235:genetics; D057185:Sedentary Behavior; D015398:Signal Transduction; D060225:Tetraspanin 28 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000097:blood / Q000235:genetics; D000099177:Tsg101 Protein
chemical_list: D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D035683:MicroRNAs; D049031:Sarcoglycans; D060225:Tetraspanin 28; D014157:Transcription Factors; D000099177:Tsg101 Protein; C554798:CD81 protein, human; C548234:MIRN133 microRNA, human; C505362:MIRN16 microRNA, human; C546087:MIRN206 microRNA, human; C540193:MIrn181 microRNA, human