Skeletal muscle releases extracellular vesicles with distinct protein and miRNA signatures that accumulate and function within the muscle microenvironment
Skeletal muscle releases extracellular vesicles with distinct protein and miRNA signatures that accumulate and function within the muscle microenvironment
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骨骼肌释放具有独特蛋白质和 miRNA 特征的细胞外囊泡，这些囊泡在肌肉微环境中积累和发挥作用
DOI：
10.1101/2021.11.30.470551
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Yoshio Yamauchi
中科院分区：
文献类型：
--
作者：
Sho Watanabe;Yuri Sudo;Satoshi Kimura;Kenji Tomita;Makoto Noguchi;Hidetoshi Sakurai;Makoto Shimizu;Yu Takahashi;Ryuichiro Sato;Yoshio Yamauchi
细胞外囊泡（EVs）含有多种调节分子，并介导细胞间的通讯。尽管EV从各种细胞类型（包括骨骼肌细胞）分泌并存在于血液中，但它们的身份在体内的特征很差，限制了它们在血液中起源的鉴定。由于骨骼肌是身体中最大的器官，因此它可以作为其来源对循环EV做出重大贡献。然而，由于缺乏明确的标志物，区分SkM-EV与其他，骨骼肌是否释放EV体内和骨骼肌衍生的EV（SkM-EV）占血浆EV的多少仍然知之甚少。在这项工作中，我们对从C2 C12细胞和人iPS细胞衍生的肌细胞释放的EV进行了定量蛋白质组学分析，并鉴定了标记SkM-EV的潜在标记蛋白。我们鉴定的这些标记物适用于SkM-EV的体内追踪。结果表明，在小鼠的对照和运动条件下，骨骼肌仅对血浆EV作为其来源做出微小贡献。另一方面，我们证明了SkM-EV集中在骨骼肌中。此外，我们发现，EVS高度富集肌肉特异性miRNA，并抑制配对盒转录因子Pax 7的表达，Pax 7是肌生成的主要调节因子。总之，我们的研究结果表明，骨骼肌在体内释放具有不同蛋白质和miRNA谱的外泌体样小EV，并且SkM-EV主要在它们积累的肌肉微环境中发挥作用。
Extracellular vesicles (EVs) contain various regulatory molecules and mediate intercellular communications. Although EVs are secreted from various cell types, including skeletal muscle cells, and present in the blood, their identity is poorly characterizedin vivo, limiting the identification of their origin in the blood. Since the 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 SkM-EVs from others, whether the skeletal muscle releases EVsin vivoand how much the skeletal muscle-derived EVs (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 toin vivotracking 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 factorPax7, a master regulator for myogenesis. Taken together, our findings reveal that the skeletal muscle releases exosome-like small EVs with distinct protein and miRNA profilesin vivoand that SkM-EVs mainly play a role within the muscle microenvironment where they accumulate.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
14.9
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.
DOI：
10.1073/pnas.2016112117
发表时间：
2020-12-08
影响因子：
11.1
作者：
Castano, Carlos;Mirasierra, Mercedes;Parrizas, Marcelina
通讯作者：
Parrizas, Marcelina
影响因子：
16
作者：
Brahmer, Alexandra;Neuberger, Elmo;Kraemer-Albers, Eva-Maria
通讯作者：
Kraemer-Albers, Eva-Maria