Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30

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) der...

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Main Authors: Di Gu, Xiangyu Zou, Guanqun Ju, Guangyuan Zhang, Erdun Bao, Yingjian Zhu
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/2093940
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author Di Gu
Xiangyu Zou
Guanqun Ju
Guangyuan Zhang
Erdun Bao
Yingjian Zhu
author_facet Di Gu
Xiangyu Zou
Guanqun Ju
Guangyuan Zhang
Erdun Bao
Yingjian Zhu
author_sort Di Gu
collection DOAJ
description 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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spelling doaj-art-3fc99d5324424baaace99f42e65c8eb02025-08-20T03:55:36ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/20939402093940Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30Di Gu0Xiangyu Zou1Guanqun Ju2Guangyuan Zhang3Erdun Bao4Yingjian Zhu5Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, ChinaDepartment of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, ChinaDepartment of Urology, Shanghai Children’s Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, ChinaDepartment of Urology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, ChinaDepartment of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, ChinaDepartment of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080, ChinaBackground. 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.http://dx.doi.org/10.1155/2016/2093940
spellingShingle Di Gu
Xiangyu Zou
Guanqun Ju
Guangyuan Zhang
Erdun Bao
Yingjian Zhu
Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30
Stem Cells International
title Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30
title_full Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30
title_fullStr Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30
title_full_unstemmed Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30
title_short Mesenchymal Stromal Cells Derived Extracellular Vesicles Ameliorate Acute Renal Ischemia Reperfusion Injury by Inhibition of Mitochondrial Fission through miR-30
title_sort mesenchymal stromal cells derived extracellular vesicles ameliorate acute renal ischemia reperfusion injury by inhibition of mitochondrial fission through mir 30
url http://dx.doi.org/10.1155/2016/2093940
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