The anti-oxidative role of micro-vesicles derived from human Wharton-Jelly mesenchymal stromal cells through NOX2/gp91(phox) suppression in alleviating renal ischemia-reperfusion injury in rats

Guangyuan Zhang; Xiangyu Zou; Shuai Miao; Jinjun Chen; Tao Du; Liang Zhong; Guanqun Ju; Guohua Liu; Yingjian Zhu

doi:10.1371/journal.pone.0092129

The anti-oxidative role of micro-vesicles derived from human Wharton-Jelly mesenchymal stromal cells through NOX2/gp91(phox) suppression in alleviating renal ischemia-reperfusion injury in rats

PLoS One. 2014 Mar 17;9(3):e92129. doi: 10.1371/journal.pone.0092129. eCollection 2014.

Authors

Guangyuan Zhang¹, Xiangyu Zou¹, Shuai Miao¹, Jinjun Chen², Tao Du³, Liang Zhong⁴, Guanqun Ju¹, Guohua Liu¹, Yingjian Zhu¹

Affiliations

¹ Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Shanghai Key Laboratory of Tissue Engineering, Tissue Engineering Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Urology, Henan Provincial People's Hospital, Zhengzhou, China; Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Urology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Oxidative stress is known as one of the main contributors in renal ischemia/reperfusion injury (IRI). Here we hypothesized that Micro-vesicles (MVs) derived from human Wharton Jelly mesenchymal stromal cells (hWJMSCs) could protect kidney against IRI through mitigating oxidative stress. MVs isolated from hWJMSCs conditioned medium were injected intravenously in rats immediately after unilateral kidney ischemia for 60 min. The animals were sacrificed at 24 h, 48 h and 2 weeks respectively after reperfusion. Our results show that the expression of NOX2 and reactive oxygen species (ROS) in injured kidney tissues was declined and the oxidative stress was alleviated in MVs group at 24 h and 48 h in parallel with the reduced apoptosis and enhanced proliferation of cells. IRI-initiated fibrosis was abrogated by MVs coincident with renal function amelioration at 2 weeks. NOX2 was also found down-regulated by MVs both in human umbilical vein endothelial cells (HUVEC) and NRK-52E cell line under hypoxia injury model in vitro. In conclusion, a single administration of hWJMSC-MVs might protect the kidney by alleviation of the oxidative stress in the early stage of kidney IRI through suppressing NOX2 expression. Moreover, it could reduce the fibrosis and improved renal function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants / pharmacology
Antioxidants / therapeutic use*
Apoptosis / drug effects
Cell Proliferation / drug effects
Cell Separation
Cell-Derived Microparticles / metabolism*
Cell-Derived Microparticles / ultrastructure
Disease Models, Animal
Down-Regulation / drug effects
Human Umbilical Vein Endothelial Cells / cytology
Humans
Hypoxia / complications
Hypoxia / pathology
Hypoxia / physiopathology
Kidney / blood supply*
Kidney / enzymology
Kidney / pathology
Kidney / physiopathology
Kidney Function Tests
Male
Membrane Glycoproteins / metabolism*
Mesenchymal Stem Cells / cytology*
Mesenchymal Stem Cells / drug effects
NADPH Oxidase 2
NADPH Oxidases / metabolism*
Oxidative Stress / drug effects
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Reperfusion Injury / complications
Reperfusion Injury / drug therapy*
Reperfusion Injury / pathology
Reperfusion Injury / physiopathology
Reperfusion Injury / therapy
Wharton Jelly / cytology*

Substances

Antioxidants
Membrane Glycoproteins
Reactive Oxygen Species
Cybb protein, rat
NADPH Oxidase 2
NADPH Oxidases

Grants and funding

This study is supported by grants from the Research Program of Science and Technology Commission of Shanghai Municipality (10411967200) and Shanghai Song-Jiang Health Bureau (2011PD06) and National Natural Science Foundation of China(81170642) and Shanghai Shen Kang Plat-form Grant (SHDC12007206). The funders had no role instudy design, data collection and analysis, decision to publish, or preparation of the manuscript.