骨骼肌
肌发生
心肌细胞
细胞生物学
生物
C2C12型
外体
微泡
小RNA
解剖
基因
生物化学
作者
Sho Watanabe,Yuri Sudo,Takumi Makino,Satoshi Kimura,Kenji Tomita,Makoto Noguchi,Hiroyuki Sakurai,Makoto Shimizu,Yu Takahashi,Ryuichiro Sato,Yoshio Yamauchi
出处
期刊:PNAS nexus
[Oxford University Press]
日期:2022-08-26
卷期号:1 (4)
被引量:14
标识
DOI:10.1093/pnasnexus/pgac173
摘要
Extracellular vesicles (EVs) contain various regulatory molecules and mediate intercellular communications. Although EVs are secreted from various cell types, including skeletal muscle cells, and are present in the blood, their identity is poorly characterized in vivo, limiting the identification of their origin in the blood. Since skeletal muscle is the largest organ in the body, it could substantially contribute to circulating EVs as their source. However, due to the lack of defined markers that distinguish skeletal muscle-derived EVs (SkM-EVs) from others, whether skeletal muscle releases EVs in vivo and how much SkM-EVs account for plasma EVs remain poorly understood. In this work, we perform quantitative proteomic analyses on EVs released from C2C12 cells and human iPS cell-derived myocytes and identify potential marker proteins that mark SkM-EVs. These markers we identified apply to in vivo tracking of SkM-EVs. The results show that skeletal muscle makes only a subtle contribution to plasma EVs as their source in both control and exercise conditions in mice. On the other hand, we demonstrate that SkM-EVs are concentrated in the skeletal muscle interstitium. Furthermore, we show that interstitium EVs are highly enriched with the muscle-specific miRNAs and repress the expression of the paired box transcription factor Pax7, a master regulator for myogenesis. Taken together, our findings confirm previous studies showing that skeletal muscle cells release exosome-like EVs with specific protein and miRNA profiles in vivo and suggest that SkM-EVs mainly play a role within the muscle microenvironment where they accumulate.
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