Hypoxia-induced extracellular vesicles mediate protection of remote ischemic preconditioning for renal ischemia-reperfusion injury

被引:19
作者
Zhang, Guangyuan [1 ]
Yang, Yu [1 ]
Huang, Yeqing [1 ]
Zhang, Lei [1 ]
Ling, Zhixin [1 ]
Zhu, Yingjian [2 ]
Wang, Feng [3 ]
Zou, Xiangyu [2 ]
Chen, Ming [1 ]
机构
[1] Southeast Univ, Zhongda Hosp, Dept Urol, 87 Dingjia Qiao Rd, Nanjing 210009, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Urol, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China
[3] Shanghai Jiao Tong Univ, Dept Nephrol & Rheumatol, Affiliated Peoples Hosp 6, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
Extracellular vesicles; Remote ischemic preconditioning; Renal tubular epithelial cells; Hypoxia; Kidney ischemia-reperfusion injury; ACUTE KIDNEY INJURY; ISCHEMIA/REPERFUSION INJURY; CARDIAC-SURGERY; CELL-SURVIVAL; MICROVESICLES; HEART; TRIAL;
D O I
10.1016/j.biopha.2017.03.096
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Remote ischemic preconditioning (rIPC) is a reliable strategy for prevention of injury to various organs. However the mechanism by which it does so is still unclear. In the present study, serum and EVs isolated from ischemic preconditioned right renal venous perfusates were injected into rats with ischemia-reperfusion- injured kidneys immediately after reperfusion. The animals were killed 24 h later. Tubular scores and renal function were tested to evaluate the therapeutic effects. To further explore the underlying mechanism, HK-2 cells derived EVs under hypoxia were also administrated to rats with left kidney IRI. Results showed that transient ischemia of the right kidney induced renal tubular epithelial cells to release functional extracellular vesicles (EVs), which were found to alleviate left kidney ischemic reperfusion injury (IRI) by circulation and the EV-depleted serum lost this property. Further, human kidney cells (HK2) were cultured under hypoxic conditions to generate EVs in vitro. These EVs also showed obvious therapeutic effects for renal IRI. Our results suggested that remote ischemic preconditioning plays a therapeutic role in renal IRI through EVs induced by hypoxia. (C) 2017 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:473 / 478
页数:6
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