Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30.
Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30.
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间充质基质细胞衍生的细胞外囊泡通过 miR-30 抑制线粒体裂变改善急性肾缺血再灌注损伤
DOI：
10.1155/2016/2093940
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发表时间：
2016
影响因子：
4.3
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Gu D;Zou X;Ju G;Zhang G;Bao E;Zhu Y
背景。线粒体分裂的失控是缺血再灌注损伤（IRI）的主要原因之一，间充质基质细胞（MSC）衍生的细胞外囊泡被认为是一种潜在的治疗方法。在这里，我们假设源自人沃顿胶间充质基质细胞 (hWJMSC) 的细胞外囊泡 (EV) 通过 miR-30b/c/d 抑制线粒体裂变来改善急性肾 IRI。方法。在单侧肾切除和肾蒂闭塞45分钟后立即将从MCS条件培养基中分离的EV静脉注射到大鼠体内。再灌注后24小时处死动物并收集样品。 MitoTracker 红染色用于观察线粒体的形态。通过蛋白质印迹法测量DRP1的表达。通过 qRT-PCR 评估 EV 和大鼠肾小管上皮细胞中的 miR-30。通过免疫染色鉴定细胞凋亡途径。结果。我们发现受损肾组织中 miR-30 的表达下降，线粒体动力学转向裂变。但在 EV 组中，它们均得到恢复，同时细胞凋亡减少。更重要的是，当使用miR-30 antagomir来降低miRNA水平时，EV的所有相关效应均显着降低。结论。单次施用 hWJMSC-EV 可以通过 miR-30 抑制线粒体裂变，保护肾脏免受 IRI 影响。
Background. The immoderation of mitochondrial fission is one of the main contributors in ischemia reperfusion injury (IRI) and mesenchymal stromal cells (MSCs) derived extracellular vesicles have been regarded as a potential therapy method. Here, we hypothesized that extracellular vesicles (EVs) derived from human Wharton Jelly mesenchymal stromal cells (hWJMSCs) ameliorate acute renal IRI by inhibiting mitochondrial fission through miR-30b/c/d. Methods. EVs isolated from the condition medium of MCS were injected intravenously in rats immediately after monolateral nephrectomy and renal pedicle occlusion for 45 minutes. Animals were sacrificed at 24 h after reperfusion and samples were collected. MitoTracker Red staining was used to see the morphology of the mitochondria. The expression of DRP1 was measured by western blot. miR-30 in EVs and rat tubular epithelial cells was assessed by qRT-PCR. Apoptosis pathway was identified by immunostaining. Results. We found that the expression of miR-30 in injured kidney tissues was declined and mitochondrial dynamics turned to fission. But they were both restored in EVs group in parallel with reduced cell apoptosis. What is more, when the miR-30 antagomirs were used to reduce the miRNA levels, all the related effects of EVs reduced remarkably. Conclusion. A single administration of hWJMSC-EVs could protect the kidney from IRI by inhibition of mitochondrial fission via miR-30.
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影响因子：
3.7
作者：
Collino F;Deregibus MC;Bruno S;Sterpone L;Aghemo G;Viltono L;Tetta C;Camussi G
通讯作者：
Camussi G
影响因子：
13.6
作者：
Ishani, Areef;Xue, Jay L.;Collins, Allan J.
通讯作者：
Collins, Allan J.
影响因子：
6.1
作者：
Gatti, Stefano;Bruno, Stefania;Camussi, Giovanni
通讯作者：
Camussi, Giovanni
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
影响因子：
4
作者：
Lindoso, Rafael S.;Collino, Federica;Camussi, Giovanni
通讯作者：
Camussi, Giovanni