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

• Published in: PloS one 2015-05, Vol.10 (5), p.e0125094-e0125094
• Main Authors: Guescini, Michele, Canonico, Barbara, Lucertini, Francesco, Maggio, Serena, Annibalini, Giosué, Barbieri, Elena, Luchetti, Francesca, Papa, Stefano, Stocchi, Vilberto
• Format: Article
• Language: English
• Subjects: Adult; Aerobics; Analysis; Autocrine signalling; Biomarkers; Cardiorespiratory fitness; CD81 antigen; Cell Communication; Cell cycle; Centrifugation, Density Gradient; Communication; Cytokines; Density gradients; Deoxyribonucleic acid; DNA; DNA-Binding Proteins - blood; DNA-Binding Proteins - genetics; Endosomal Sorting Complexes Required for Transport - blood; Endosomal Sorting Complexes Required for Transport - genetics; Exercise; Exosomes - chemistry; Exosomes - metabolism; Extracellular vesicles; Extracellular Vesicles - chemistry; Extracellular Vesicles - metabolism; Gene expression; Gene Expression Regulation; Homeostasis; Hormones; Humans; Lipids; Lung cancer; Male; MicroRNA; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; miRNA; Muscle contraction; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; Paracrine signalling; Physical exercise; Physical fitness; Plasma; Proteins; Researchers; Ribonucleic acid; RNA; Sarcoglycans - blood; Sarcoglycans - genetics; Science; Sedentary Lifestyle; Signal Transduction; Skeletal muscle; Studies; Tetraspanin 28 - genetics; Tetraspanin 28 - metabolism; Transcription Factors - blood; Transcription Factors - genetics; Vesicles
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125094

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.