Zhou Min, Li Bingshu, Liu Cheng, Hu Ming, Tang Jianming, Min Jie, Cheng Jianhong, Hong Li
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China.
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China.
Int Immunopharmacol. 2021 Dec;101(Pt B):108223. doi: 10.1016/j.intimp.2021.108223. Epub 2021 Oct 8.
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 vivo experiments 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.
耻骨尾骨肌损伤可导致压力性尿失禁（SUI）。M2巨噬细胞在受损肌肉再生过程中的成肌细胞分化中起关键作用。然而，其潜在机制仍不清楚。近来，外泌体因其介导细胞间通讯而受到越来越多的关注。在本研究中，我们发现M2巨噬细胞在体内损伤后第5天（VD5）广泛浸润耻骨尾骨肌。然后，用M2巨噬细胞衍生的外泌体（M2-EXO）处理C2C12成肌细胞，结果显示这些外泌体可促进肌管形成。MiR-501被鉴定为选择性装载于M2-EXO中的丰富微RNA（miRNA）之一，随后证实其通过靶向YY1促进C2C12成肌细胞分化。此外，体内实验表明M2-EXO可改善炎性细胞浸润，并对SUI模型中受损的耻骨尾骨肌具有治疗作用。总之，我们目前的结果为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可能是促进从包括SUI在内的肌肉损伤引起的疾病中恢复的潜在治疗方法。
