M2 Macrophage-derived exosomal miR-501 contributes to pubococcygeal muscle regeneration.

M2 Macrophage-derived exosomal miR-501 contributes to pubococcygeal muscle regeneration.
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M2 巨噬细胞衍生的外泌体 miR-501 有助于耻骨尾骨肌再生。

DOI:
10.1016/j.intimp.2021.108223
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发表时间:
2021-10
影响因子:
5.6
通讯作者:
Jianhong Cheng
Jianhong Cheng
中科院分区:
医学2区
文献类型:
--
作者:
Min Zhou;Jianming Tang;Jie Min;Bingshu Li;Ming Hu;Li Hong;Cheng Liu;Jianhong Cheng

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耻骨尾骨肌损伤可导致压力性尿失禁(SUI)。M2巨噬细胞在损伤肌肉再生过程中的成肌细胞分化中起着至关重要的作用。然而,其潜在机制仍不清楚。近年来,外来体由于其介导细胞间通讯而引起了越来越多的关注。在这项研究中,我们发现M2巨噬细胞广泛浸润的耻骨尾骨肌损伤后第5天(VD 5)在体内。然后,用M2巨噬细胞来源的外泌体(M2-EXO)处理C2 C12成肌细胞,结果显示这些外泌体可以促进肌管形成。MiR-501被鉴定为选择性装载在M2-EXO中的丰富的microRNA(miRNAs)之一,并且随后被证实通过靶向YY 1促进C2 C12成肌细胞分化。此外,体内实验表明,M2-EXO改善了SUI模型中的炎性细胞浸润,并对损伤的耻尾肌具有治疗作用。总的来说,我们目前的研究结果为M2巨噬细胞的促肌生成机制提供了新的见解,并证明M2巨噬细胞外泌体miR-501可能代表了一种潜在的治疗方法,可以促进肌肉损伤引起的疾病(包括SUI)的恢复。
Pubococcygeal muscle injury can lead to stress urinary incontinence (SUI). M2 macrophages play a crucial role in myoblast differentiation during injured muscle regeneration. However, the underlying mechanism remains unclear. Recently, exosomes have attracted increasing attention due to their mediation of cell-to-cell communication. In this study, we found that M2 macrophages extensively infiltrated the pubococcygeal muscle on day 5 after injury (VD5)in vivo. Then, C2C12 myoblasts were treated with M2 macrophage-derived exosomes (M2-EXO) and the results revealed that these exosomes could promote myotube formation. MiR-501 was identified as one of the abundant microRNAs (miRNAs) selectively loaded in M2-EXO, and subsequently confirmed to promote C2C12 myoblast differentiation by targeting YY1. Moreover,in vivoexperiments showed that M2-EXO improves the inflammatory cell infiltration and have a therapeutic effect on damaged pubococcygeal muscle in SUI models. Collectively, our present results provide new insights into the promyogenic mechanism of M2 macrophages and prove that M2 macrophage exosomal miR-501 may represent a potential therapeutic to promote recovery from diseases caused by muscle injury, including SUI.
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