MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction.
MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction.
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MicroRNA-133过表达促进间充质干细胞对急性心肌梗死的治疗效果。
DOI：
10.1186/s13287-017-0722-z
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发表时间：
2017-11-25
影响因子：
7.5
通讯作者：
Shen Z
中科院分区：
文献类型：
--
作者：
Chen Y;Zhao Y;Chen W;Xie L;Zhao ZA;Yang J;Chen Y;Lei W;Shen Z
我们的研究目的是评估过表达miR-133的间充质干细胞（MSC）对急性心肌梗死的治疗效果和机制。采用全骨髓贴壁培养法分离纯化大鼠MSCs。转染 miR-133 的 agomir 或 antagomir 后，收集 MSC 以检测细胞活力、细胞凋亡和细胞周期进展。同时，从上清液中分离出外泌体，用于分析旁分泌miR-133。对于体内研究，MSC 中 miR-133 的组成型激活是通过慢病毒介导的 miR-133 过表达来实现的。通过结扎左冠状动脉前降支建立大鼠心肌梗死模型，同时将对照MSC（载体-MSC）或miR-133过表达的MSC（miR-133-MSC）注射到心肌梗死周围区域。随后，在梗死后第7天和第28天通过超声心动图评估心肌功能。最后在第7天和第28天收集梗塞心脏用于心肌梗塞大小测量和snail 1表达检测。转染miR-133 agomir后，缺氧诱导的MSCs凋亡明显减少，总聚ADP核糖聚合酶蛋白表达增强，而转染miR-133 antagomir的MSCs凋亡率增加。然而，在对照、miR-133过表达和miR-133干扰的MSC中没有观察到细胞活力和细胞周期分布的变化。重要的是，与注射载体-MSC 的大鼠相比，移植 miR-133-MSC 的大鼠在急性心肌梗死后显示出更多改善的心脏功能。进一步的研究表明，snail 1 的心脏表达被邻近的 miR-133 过度表达的 MSC 显着抑制，并且注射 miR-133-MSC 的大鼠心脏的炎症水平和梗塞面积均下降。 miR-133-MSCs 明显改善心肌梗死大鼠模型的心功能。移植过度表达 miR-133 的 MSC 为心脏修复和调节心脏相关疾病提供了有效的策略。本文的在线版本 (doi:10.1186/s13287-017-0722-z) 包含补充材料，可供授权用户使用。
Our study aim was to evaluate the therapeutic efficacy and mechanisms of miR-133-overexpressing mesenchymal stem cells (MSCs) on acute myocardial infarction. Rat MSCs were isolated and purified by whole bone marrow adherent culturing. After transfection with the agomir or antagomir of miR-133, MSCs were collected for assay of cell vitality, apoptosis, and cell cycle progression. At the same time, exosomes were isolated from the supernatant to analyze the paracrine miR-133. For in-vivo studies, constitutive activation of miR-133 in MSCs was achieved by lentivirus-mediated miR-133 overexpression. A rat myocardial infarction model was created by ligating the left anterior descending coronary artery, while control MSCs (vector-MSCs) or miR-133-overexpressed MSCs (miR-133-MSCs) were injected into the zone around the myocardial infarction. Subsequently, myocardial function was evaluated by echocardiography on days 7 and 28 post infarction. Finally the infarcted hearts were collected on days 7 and 28 for myocardial infarct size measurement and detection of snail 1 expression. Hypoxia-induced apoptosis of MSCs obviously reduced, along with enhanced expression of total poly ADP-ribose polymerase protein, after miR-133 agomir transfection, while the apoptosis rate increased in MSCs transfected with miR-133 antagomir. However, no change in cell viability and cell-cycle distribution was observed in control, miR-133-overexpressed, and miR-133-interfered MSCs. Importantly, rats transplanted with miR-133-MSCs displayed more improved cardiac function after acute myocardial infarction, compared with those that received vector-MSC injection. Further studies indicated that cardiac expression of snail 1 was significantly repressed by adjacent miR-133-overexpressing MSCs, and both the inflammatory level and the infarct size decreased in miR-133-MSC-injected rat hearts. miR-133-MSCs obviously improved cardiac function in a rat model of myocardial infarction. Transplantation of miR-133-overexpressing MSCs provides an effective strategy for cardiac repair and modulation of cardiac-related diseases. The online version of this article (doi:10.1186/s13287-017-0722-z) contains supplementary material, which is available to authorized users.
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作者：
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