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

机译:肌肉释放血液中携带miRNA的Alpha-Sarcoglycan阳性胞外小泡

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摘要

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.
机译:在过去的几年中,骨骼肌已经成为一种重要的分泌器官,产生可溶因子,称为肌动蛋白,发挥自分泌,旁分泌或内分泌作用。此外,最近的研究表明,肌肉会响应体育锻炼将microRNA释放到血液中。这些microRNA会影响靶细胞,例如激素和细胞因子。目前,微RNA分泌的潜在机制尚不明确。在这里,我们研究了肌肉组织是否释放出细胞外囊泡(EVs),这些细胞在生理条件下(例如体育锻炼)在血液中携带microRNA。通过对久坐和身体健康的年轻人血浆的密度梯度分离,我们发现EV对TSG101和α-糖聚糖(SGCA)呈阳性,而对miR-206富集。细胞计数分析表明,SGCA +电动汽车占总数的1–5%,这些电动汽车中60–65%的外泌体标记CD81也是阳性的。此外,与总血浆电动车相比,SGCA免疫捕获的电动车亚群显示出更高水平的miR-206 / miR16比。最后,在有氧适应性和肌肉特异性miRNA之间发现显着正相关,并且在急性运动后EV miR-133b和-181a-5p显着上调。因此,我们的研究提出,电动汽车是一种可能参与肌肉重塑和体内平衡的新型肌肉交流手段。

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