Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22.
Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22.
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DOI：
10.1371/journal.pone.0088685
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ashraf M
中科院分区：
文献类型：
--
作者：
Feng Y;Huang W;Wani M;Yu X;Ashraf M
间充质干细胞（MSCs）在缺血性心脏病的治疗中具有潜在的应用前景。除了分化特性外，MSCs还通过分泌旁分泌因子保护缺血心肌细胞。在这项研究中，我们发现MSCs在缺血预处理（ExoIPC）后分泌富集miR-22的外泌体，并被动员到心肌细胞中，减少心肌细胞因缺血而导致的凋亡。有趣的是，通过延时成像，我们首次捕获了装载miR-22的外泌体从细胞质到细胞外空间的动态脱落。此外，miR-22的抗凋亡作用是通过直接靶向甲基CpG结合蛋白2 （Mecp2）介导的。体内数据显示，ExoIPC的递送可显著减少心脏纤维化。我们的数据确定了ExoIPC通过miR-22靶向Mecp2治疗心脏病的显着益处。
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 (ExoIPC) 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 ExoIPC significantly reduced cardiac fibrosis. Our data identified a significant benefit of ExoIPC for the treatment of cardiac diseases by targeting Mecp2 via miR-22.
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影响因子：
21.3
作者：
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通讯作者：
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影响因子：
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