Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect Against Acute Kidney Injury Through Anti-Oxidation by Enhancing Nrf2/ARE Activation in Rats

被引:136
作者
Zhang, Guangyuan [1 ]
Zou, Xiangyu [2 ]
Huang, Yeqing [1 ]
Wang, Feng [3 ]
Miao, Shuai [2 ]
Liu, Guohua [2 ]
Chen, Ming [1 ]
Zhu, Yingjian [4 ]
机构
[1] Southeast Univ, Sch Med, Zhongda Hosp, Dept Urol, Nanjing 210009, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Sch Med, Dept Urol, Shanghai 200072, Peoples R China
[3] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Nephrol & Rheumatol, Shanghai 200072, Peoples R China
[4] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Urol, Shanghai 200072, Peoples R China
基金
中国国家自然科学基金;
关键词
Mesenchymal stromal cells; Extracellular vesicles; Acute kidney injury; Ischemia-reperfusion injury; Nrf2; HO-1; ISCHEMIA-REPERFUSION INJURY; ACUTE TUBULAR INJURY; OXIDATIVE STRESS; SIGNALING PATHWAY; CARDIAC-SURGERY; MECHANISMS; EXPRESSION; APOPTOSIS; NECROSIS; OUTCOMES;
D O I
10.1159/000443413
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Background/Aims: Anti-oxidation is an effective strategy for curing acute kidney injury (AKI). Herein, we suggest that extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) might play an anti-oxidative role by enhancing Nrf2/ARE activation in AKI. Methods: EVs isolated from the conditioned medium of human Wharton's Jelly mesenchymal stromal cells and human foreskin fibroblast were intravenously injected in rats immediately after 45 min of unilateral kidney ischemia. Animals were sacrificed 24 h after injury. Results: Results showed that renal tubular injury was alleviated and renal function was improved by MSC-EVs. Cell apoptosis and sNGAL levels, which reflect kidney cell injury, were reduced. Moreover, MSC-EVs decreased oxidative stress in injured kidney tissues and NRK-52E cells under hypoxia injury. Nrf2/antioxidant response element (ARE) enhancement and HO-1 up-regulation were further observed after MSC-EV treatment both in vivo and in vitro. Conclusions: MSC-EVs may protect against AKI possibly through anti-oxidation by enhancing Nrf2/ARE activation. (C) 2016 The Author(s) Published by S. Karger AG, Basel
引用
收藏
页码:119 / 128
页数:10
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