title: 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.
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.
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Miao
authors.affiliation: Shanghai Key Laboratory of Tissue Engineering, Tissue Engineering Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Du
authors.affiliation: Department of Urology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guanqun
authors.initials: G
authors.lastname: Ju
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000648:ultrastructure; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D059631:Wharton Jelly / Q000166:cytology*
chemical_list: D000975:Antioxidants; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases