miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage.
miR-93-5p-Containing Exosomes Treatment Attenuates Acute Myocardial Infarction-Induced Myocardial Damage.
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含miR-93-5p的外泌体治疗可减轻急性心肌梗死引起的心肌损伤
DOI：
10.1016/j.omtn.2018.01.010
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发表时间：
2018-06-01
期刊：
影响因子：
--
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Liu J;Jiang M;Deng S;Lu J;Huang H;Zhang Y;Gong P;Shen X;Ruan H;Jin M;Wang H
脂肪源性基质细胞（ADSCs）被认为是一种有吸引力的治疗工具。越来越多的证据表明，ADSCs的愈合作用主要与旁分泌作用有关，而不是转分化。数据显示，急性心肌梗死（AMI）后miR-93-5p的表达具有心脏保护作用。为了确定形成ADSCs的mir -93-5p包封外泌体是否具有更好的心脏保护作用，我们在临床水平上研究了炎症因子和miR-30d-5p的表达。建立AMI大鼠模型和体外缺氧H9c2细胞模型，研究miR-93-5p在缺血心脏损伤中的保护机制。结果显示，AMI患者和动物模型中炎症细胞因子和miR-93-5p的表达均升高。此外，使用adsc衍生的含有mir -93-5p的外泌体治疗比简单的外泌体处理对梗死诱导的心肌损伤具有更大的保护作用。此外，体外实验证实，miR-93-5p的表达可以分别靶向Atg7和toll样受体4 (TLR4)，显著抑制缺氧诱导的自噬和炎症细胞因子的表达，并通过Atg7或TLR4过表达得到证实。结果还表明，自噬激活可以间接促进炎症细胞因子的表达。综上所述，这些结果表明，mir -93-5p增强的adsc来源的外泌体通过抑制自噬和炎症反应来预防心脏损伤。
Adipose-derived stromal cells (ADSCs) have been considered as an attractive therapeutic tool. Accumulating evidence indicates that the healing effects of ADSCs are mainly related to paracrine action rather than transdifferentiation. Data show that the expression of miR-93-5p has a cardio-protective effect after acute myocardial infarction (AMI). To identify whether miR-93-5p-encapsulating exosomes that form ADSCs have a better cardio-protective effect, we investigated the inflammatory factors and miR-30d-5p expression in clinical levels. A rat model of AMI and an in vitro model of hypoxic H9c2 cells were established to study the protective mechanism of miR-93-5p in ischemia-induced cardiac injury. The results show that the expression of inflammatory cytokines and miR-93-5p were increased following AMI in both patients and animal models. Moreover, treatment with ADSC-derived miR-93-5p-containing exosomes has a greater protective effect on infarction-induced myocardial damage than simple exosome processing. Furthermore, in vitro experiments confirmed that the expression of miR-93-5p can significantly suppress hypoxia-induced autophagy and inflammatory cytokine expression by targeting Atg7 and Toll-like receptor 4 (TLR4), respectively, and was confirmed with Atg7 or TLR4 overexpression. The results also show that autophagy activation can promote inflammatory cytokine expression indirectly. Taken together, these results suggest that the miR-93-5p-enhanced ADSC-derived exosomes prevent cardiac injury by inhibiting autophagy and the inflammatory response.
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DOI：
10.1016/j.bbadis.2014.10.008
发表时间：
2015-01
影响因子：
6.2
作者：
Ailawadi, Shaina;Wang, Xiaohong;Gu, Haitao;Fan, Guo-Chang
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影响因子：
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影响因子：
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影响因子：
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