Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells
Circulating myocardial microRNAs from infarcted hearts are carried in exosomes and mobilise bone marrow progenitor cells
复制标题
来自梗塞心脏的循环心肌 microRNA 被外泌体携带并动员骨髓祖细胞
DOI：
10.1038/s41467-019-08895-7
复制
发表时间：
2019-02-27
影响因子：
16.6
通讯作者：
Qin, Gangjian
中科院分区：
文献类型：
--
作者：
Cheng, Min;Yang, Junjie;Qin, Gangjian
心肌microRNA（myo-miR）在急性心肌梗死（AMI）后被释放到循环中。然而，它们如何影响远程器官在很大程度上是未知的。在这里，我们表明，循环myo-miRs携带在外来体中，并介导缺血性心脏和骨髓（BM）之间的功能串扰。在小鼠中，我们发现AMI伴随着myo-miR循环水平的增加，其中miR-1，208和499主要存在于循环外泌体中，而miR-133存在于非外泌体组分中。Myo-miR被选择性地输入到外周器官并且优先输入到BM。外泌体介导myo-miR向BM单核细胞（MNC）的转移，其中myo-miR下调CXCR 4表达。将从AMI小鼠分离的外泌体注射到野生型小鼠中下调BM-MNC中的CXCR 4表达并增加循环祖细胞的数量。因此，我们提出，在循环外泌体中携带的myo-miR允许对心脏损伤的全身性反应，这可以用于心脏修复。
Myocardial microRNAs (myo-miRs) are released into the circulation after acute myocardial infarction (AMI). How they impact remote organs is however largely unknown. Here we show that circulating myo-miRs are carried in exosomes and mediate functional crosstalk between the ischemic heart and the bone marrow (BM). In mice, we find that AMI is accompanied by an increase in circulating levels of myo-miRs, with miR-1, 208, and 499 predominantly in circulating exosomes and miR-133 in the non-exosomal component. Myo-miRs are imported selectively to peripheral organs and preferentially to the BM. Exosomes mediate the transfer of myo-miRs to BM mononuclear cells (MNCs), where myo-miRs downregulate CXCR4 expression. Injection of exosomes isolated from AMI mice into wild-type mice downregulates CXCR4 expression in BM-MNCs and increases the number of circulating progenitor cells. Thus, we propose that myo-miRs carried in circulating exosomes allow a systemic response to cardiac injury that may be leveraged for cardiac repair.