CCR2 Positive Exosome Released by Mesenchymal Stem Cells Suppresses Macrophage Functions and Alleviates Ischemia/Reperfusion-Induced Renal Injury

Mesenchymal stem cells (MSCs) derived exosomes have been shown to have protective effects on the kidney in ischemia/reperfusion-induced renal injury. However, the key components in the exosomes and their potential mechanisms for the kidney protective effects are not well understood. In our current s...

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Main Authors: Bing Shen, Jun Liu, Fang Zhang, Yong Wang, Yan Qin, Zhihua Zhou, Jianxin Qiu, Yu Fan
Format: Article
Language:English
Published: Hindawi Limited 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/1240301
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spelling doaj-6021340320c548338f668834be4865f32020-11-24T23:59:44ZengHindawi LimitedStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/12403011240301CCR2 Positive Exosome Released by Mesenchymal Stem Cells Suppresses Macrophage Functions and Alleviates Ischemia/Reperfusion-Induced Renal InjuryBing Shen0Jun Liu1Fang Zhang2Yong Wang3Yan Qin4Zhihua Zhou5Jianxin Qiu6Yu Fan7Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Urology, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, 100 Haining Road, Shanghai 200080, ChinaMesenchymal stem cells (MSCs) derived exosomes have been shown to have protective effects on the kidney in ischemia/reperfusion-induced renal injury. However, the key components in the exosomes and their potential mechanisms for the kidney protective effects are not well understood. In our current study, we focused on the abundant proteins in exosomes derived from MSCs (MSC-exo) and found that the C-C motif chemokine receptor-2 (CCR2) was expressed on MSC-exo with a high ability to bind to its ligand CCL2. We also proved that CCR2 high-expressed MSC-exo could reduce the concentration of free CCL2 and suppress its functions to recruit or activate macrophage. Further, knockdown of CCR2 expression on the MSC-exo greatly abolished these effects. Finally, we also found that CCR2 knockdown impaired the protective effects of MSC-exo for the renal ischemia/reperfusion injury in mouse. The results indicate that CCR2 expressed on MSC-exo may play a key role in inflammation regulation and renal injury repair by acting as a decoy to suppress CCL2 activity. Our study may cast new light on understanding the functions of the MSC-exo and these receptor proteins expressed on exosomes.http://dx.doi.org/10.1155/2016/1240301
collection DOAJ
language English
format Article
sources DOAJ
author Bing Shen
Jun Liu
Fang Zhang
Yong Wang
Yan Qin
Zhihua Zhou
Jianxin Qiu
Yu Fan
spellingShingle Bing Shen
Jun Liu
Fang Zhang
Yong Wang
Yan Qin
Zhihua Zhou
Jianxin Qiu
Yu Fan
CCR2 Positive Exosome Released by Mesenchymal Stem Cells Suppresses Macrophage Functions and Alleviates Ischemia/Reperfusion-Induced Renal Injury
Stem Cells International
author_facet Bing Shen
Jun Liu
Fang Zhang
Yong Wang
Yan Qin
Zhihua Zhou
Jianxin Qiu
Yu Fan
author_sort Bing Shen
title CCR2 Positive Exosome Released by Mesenchymal Stem Cells Suppresses Macrophage Functions and Alleviates Ischemia/Reperfusion-Induced Renal Injury
title_short CCR2 Positive Exosome Released by Mesenchymal Stem Cells Suppresses Macrophage Functions and Alleviates Ischemia/Reperfusion-Induced Renal Injury
title_full CCR2 Positive Exosome Released by Mesenchymal Stem Cells Suppresses Macrophage Functions and Alleviates Ischemia/Reperfusion-Induced Renal Injury
title_fullStr CCR2 Positive Exosome Released by Mesenchymal Stem Cells Suppresses Macrophage Functions and Alleviates Ischemia/Reperfusion-Induced Renal Injury
title_full_unstemmed CCR2 Positive Exosome Released by Mesenchymal Stem Cells Suppresses Macrophage Functions and Alleviates Ischemia/Reperfusion-Induced Renal Injury
title_sort ccr2 positive exosome released by mesenchymal stem cells suppresses macrophage functions and alleviates ischemia/reperfusion-induced renal injury
publisher Hindawi Limited
series Stem Cells International
issn 1687-966X
1687-9678
publishDate 2016-01-01
description Mesenchymal stem cells (MSCs) derived exosomes have been shown to have protective effects on the kidney in ischemia/reperfusion-induced renal injury. However, the key components in the exosomes and their potential mechanisms for the kidney protective effects are not well understood. In our current study, we focused on the abundant proteins in exosomes derived from MSCs (MSC-exo) and found that the C-C motif chemokine receptor-2 (CCR2) was expressed on MSC-exo with a high ability to bind to its ligand CCL2. We also proved that CCR2 high-expressed MSC-exo could reduce the concentration of free CCL2 and suppress its functions to recruit or activate macrophage. Further, knockdown of CCR2 expression on the MSC-exo greatly abolished these effects. Finally, we also found that CCR2 knockdown impaired the protective effects of MSC-exo for the renal ischemia/reperfusion injury in mouse. The results indicate that CCR2 expressed on MSC-exo may play a key role in inflammation regulation and renal injury repair by acting as a decoy to suppress CCL2 activity. Our study may cast new light on understanding the functions of the MSC-exo and these receptor proteins expressed on exosomes.
url http://dx.doi.org/10.1155/2016/1240301
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