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肌源性外泌体 miR-140-5p 通过调节肌肉卫星细胞来调节骨骼肌再生和损伤修复。

Myogenic exosome miR-140-5p modulates skeletal muscle regeneration and injury repair by regulating muscle satellite cells.

机构信息

College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China.

Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, China.

出版信息

Aging (Albany NY). 2024 Feb 29;16(5):4609-4630. doi: 10.18632/aging.205617.

Abstract

Muscle satellite cells (SCs) play a crucial role in the regeneration and repair of skeletal muscle injuries. Previous studies have shown that myogenic exosomes can enhance satellite cell proliferation, while the expression of miR-140-5p is significantly reduced during the repair process of mouse skeletal muscle injuries induced by BaCl2. This study aims to investigate the potential of myogenic exosomes carrying miR-140-5p inhibitors to activate SCs and influence the regeneration of injured muscles. Myogenic progenitor cell exosomes (MPC-Exo) and contained miR-140-5p mimics/inhibitors myogenic exosomes (MPC-Exo and MPC-Exo) were employed to treat SCs and use the model. The results demonstrate that miR-140-5p regulates SC proliferation by targeting . Upon the addition of MPC-Exo and MPC-Exo, expression in SCs significantly increased, leading to the transition of the cell cycle from G1 to S phase and an enhancement in cell proliferation. Furthermore, the therapeutic effect of MPC-Exo was validated in animal model, where the expression of muscle growth-related genes substantially increased in the gastrocnemius muscle. Our research demonstrates that MPC-Exo can effectively activate dormant muscle satellite cells, initiating their proliferation and differentiation processes, ultimately leading to the formation of new skeletal muscle cells and promoting skeletal muscle repair and remodeling.

摘要

肌卫星细胞(SCs)在骨骼肌损伤的再生和修复中起着至关重要的作用。先前的研究表明,成肌外泌体可以增强卫星细胞的增殖,而 miR-140-5p 的表达在 BaCl2 诱导的小鼠骨骼肌损伤修复过程中显著降低。本研究旨在探讨携带 miR-140-5p 抑制剂的成肌外泌体激活 SCs 并影响受损肌肉再生的潜力。使用肌源性祖细胞外泌体(MPC-Exo)和携带 miR-140-5p 模拟物/抑制剂的成肌外泌体(MPC-Exo 和 MPC-Exo)来处理 SCs 并采用该模型。结果表明,miR-140-5p 通过靶向 来调节 SC 增殖。加入 MPC-Exo 和 MPC-Exo 后,SCs 中 的表达显著增加,导致细胞周期从 G1 期向 S 期转变,细胞增殖增强。此外,在动物模型中验证了 MPC-Exo 的治疗效果,其中腓肠肌中与肌肉生长相关的基因表达显著增加。我们的研究表明,MPC-Exo 可以有效地激活休眠的肌肉卫星细胞,启动其增殖和分化过程,最终导致新的骨骼肌细胞的形成,并促进骨骼肌的修复和重塑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6154/10968704/6b2468041db7/aging-16-205617-g001.jpg

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