Exosomes Derived From Mesenchymal Stem Cells Ameliorate Renal Ischemic-Reperfusion Injury Through Inhibiting Inflammation and Cell Apoptosis

This study aimed to investigate the underlying mechanism of mesenchymal stem cells (MSCs) on protection of renal ischemia reperfusion injury (IRI). Exosomes originated from MSCs (MSC-ex) were extracted according to the instructions of Total Exosome Isolation Reagent. Rats were divided into five grou...

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Main Authors: Long Li, Rulin Wang, Yichen Jia, Ruiming Rong, Ming Xu, Tongyu Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-11-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmed.2019.00269/full
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author Long Li
Long Li
Rulin Wang
Yichen Jia
Yichen Jia
Ruiming Rong
Ruiming Rong
Ming Xu
Ming Xu
Tongyu Zhu
Tongyu Zhu
author_facet Long Li
Long Li
Rulin Wang
Yichen Jia
Yichen Jia
Ruiming Rong
Ruiming Rong
Ming Xu
Ming Xu
Tongyu Zhu
Tongyu Zhu
author_sort Long Li
collection DOAJ
description This study aimed to investigate the underlying mechanism of mesenchymal stem cells (MSCs) on protection of renal ischemia reperfusion injury (IRI). Exosomes originated from MSCs (MSC-ex) were extracted according to the instructions of Total Exosome Isolation Reagent. Rats were divided into five groups: sham-operated, IRI, MSC, MSC-ex, and MSC-ex + RNAase group. MSCs or MSC-ex were injected via carotid artery. The renal function test and pathological detection were applied to determine the renoprotection of MSC-ex on IRI. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were conducted to examine the levels of apoptosis-related proteins and inflammatory cytokines. Our results revealed that MSC-derived exosomes attenuated renal dysfunction, histologic damage, and decreased apoptosis. The expression levels of inflammatory cytokines, such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), and interferon gamma (IFN-γ), were decreased by the MSC-ex treatment. The expression levels of caspase-9, cleaved caspase-3, Bax, and Bcl-2 caused by IR were also inhibited by MSC-ex. MSC-ex + RNAase group shared the similar pattern of changes with IRI group, likely due to the ability of RNA hydrolase to eliminate the function of exosomes. Our results demonstrated that exosomes originating from MSCs have protective effects on IRI via inhibiting cell apoptosis and inflammatory responses. Out findings may provide a new insight into therapeutic mechanism of MSCs on renal IRI.
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spelling doaj.art-daae4addd3214485ac00f7cd116587d52022-12-21T19:04:40ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2019-11-01610.3389/fmed.2019.00269492274Exosomes Derived From Mesenchymal Stem Cells Ameliorate Renal Ischemic-Reperfusion Injury Through Inhibiting Inflammation and Cell ApoptosisLong Li0Long Li1Rulin Wang2Yichen Jia3Yichen Jia4Ruiming Rong5Ruiming Rong6Ming Xu7Ming Xu8Tongyu Zhu9Tongyu Zhu10Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaDepartment of Urology, Zhongshan Hospital, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Organ Transplantation, Shanghai, ChinaThis study aimed to investigate the underlying mechanism of mesenchymal stem cells (MSCs) on protection of renal ischemia reperfusion injury (IRI). Exosomes originated from MSCs (MSC-ex) were extracted according to the instructions of Total Exosome Isolation Reagent. Rats were divided into five groups: sham-operated, IRI, MSC, MSC-ex, and MSC-ex + RNAase group. MSCs or MSC-ex were injected via carotid artery. The renal function test and pathological detection were applied to determine the renoprotection of MSC-ex on IRI. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were conducted to examine the levels of apoptosis-related proteins and inflammatory cytokines. Our results revealed that MSC-derived exosomes attenuated renal dysfunction, histologic damage, and decreased apoptosis. The expression levels of inflammatory cytokines, such as interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), and interferon gamma (IFN-γ), were decreased by the MSC-ex treatment. The expression levels of caspase-9, cleaved caspase-3, Bax, and Bcl-2 caused by IR were also inhibited by MSC-ex. MSC-ex + RNAase group shared the similar pattern of changes with IRI group, likely due to the ability of RNA hydrolase to eliminate the function of exosomes. Our results demonstrated that exosomes originating from MSCs have protective effects on IRI via inhibiting cell apoptosis and inflammatory responses. Out findings may provide a new insight into therapeutic mechanism of MSCs on renal IRI.https://www.frontiersin.org/article/10.3389/fmed.2019.00269/fullmesenchymal stem cellsexosomesischemic-reperfusion injuryinflammationapoptosis
spellingShingle Long Li
Long Li
Rulin Wang
Yichen Jia
Yichen Jia
Ruiming Rong
Ruiming Rong
Ming Xu
Ming Xu
Tongyu Zhu
Tongyu Zhu
Exosomes Derived From Mesenchymal Stem Cells Ameliorate Renal Ischemic-Reperfusion Injury Through Inhibiting Inflammation and Cell Apoptosis
Frontiers in Medicine
mesenchymal stem cells
exosomes
ischemic-reperfusion injury
inflammation
apoptosis
title Exosomes Derived From Mesenchymal Stem Cells Ameliorate Renal Ischemic-Reperfusion Injury Through Inhibiting Inflammation and Cell Apoptosis
title_full Exosomes Derived From Mesenchymal Stem Cells Ameliorate Renal Ischemic-Reperfusion Injury Through Inhibiting Inflammation and Cell Apoptosis
title_fullStr Exosomes Derived From Mesenchymal Stem Cells Ameliorate Renal Ischemic-Reperfusion Injury Through Inhibiting Inflammation and Cell Apoptosis
title_full_unstemmed Exosomes Derived From Mesenchymal Stem Cells Ameliorate Renal Ischemic-Reperfusion Injury Through Inhibiting Inflammation and Cell Apoptosis
title_short Exosomes Derived From Mesenchymal Stem Cells Ameliorate Renal Ischemic-Reperfusion Injury Through Inhibiting Inflammation and Cell Apoptosis
title_sort exosomes derived from mesenchymal stem cells ameliorate renal ischemic reperfusion injury through inhibiting inflammation and cell apoptosis
topic mesenchymal stem cells
exosomes
ischemic-reperfusion injury
inflammation
apoptosis
url https://www.frontiersin.org/article/10.3389/fmed.2019.00269/full
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