缺血预处理通过miR-22靶向Mecp2，经由外泌体分泌增强干细胞的保护作用。
Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22.
作者信息
Feng Yuliang, Huang Wei, Wani Mashhood, Yu Xiyong, Ashraf Muhammad
机构信息
Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Cardiovascular Institute, Southern Medical University, Guangzhou, China ; Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
出版信息
PLoS One. 2014 Feb 18;9(2):e88685. doi: 10.1371/journal.pone.0088685. eCollection 2014.
Mesenchymal stem cells (MSCs) have potential application for the treatment of ischemic heart diseases. Besides differentiation properties, MSCs protect ischemic cardiomyocytes by secretion of paracrine factors. In this study, we found exosomes enriched with miR-22 were secreted by MSCs following ischemic preconditioning (Exo(IPC)) and mobilized to cardiomyocytes where they reduced their apoptosis due to ischemia. Interestingly, by time-lapse imaging, we for the first time captured the dynamic shedding of miR-22 loaded exosomes from cytosol to extracellular space. Furthermore, the anti-apoptotic effect of miR-22 was mediated by direct targeting of methyl CpG binding protein 2 (Mecp2). In vivo data showed that delivery of Exo(IPC) significantly reduced cardiac fibrosis. Our data identified a significant benefit of Exo(IPC) for the treatment of cardiac diseases by targeting Mecp2 via miR-22.
间充质干细胞（MSCs）在缺血性心脏病治疗中具有潜在应用价值。除了分化特性外，MSCs还通过分泌旁分泌因子来保护缺血心肌细胞。在本研究中，我们发现缺血预处理后的MSCs分泌富含miR-22的外泌体（Exo(IPC)），并转移至心肌细胞，从而减少其因缺血导致的凋亡。有趣的是，通过延时成像，我们首次捕捉到了载有miR-22的外泌体从细胞质到细胞外空间的动态释放过程。此外，miR-22的抗凋亡作用是通过直接靶向甲基化CpG结合蛋白2（Mecp2）介导的。体内数据表明，Exo(IPC)的递送显著减少了心脏纤维化。我们的数据表明，Exo(IPC)通过miR-22靶向Mecp2对心脏病治疗具有显著益处。
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