title: Hypoxia-induced extracellular vesicles mediate protection of remote ischemic preconditioning for renal ischemia-reperfusion injury.
abstract: 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 24h 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.
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China.
authors.forename: Yeqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Ling
authors.affiliation: Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Urology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: zouxiangyudy@126.com.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Urology, Zhongda Hospital, Southeast University, Nanjing, China. Electronic address: chenmingseu@126.com.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology*; D000818:Animals; D002460:Cell Line; D000067128:Extracellular Vesicles / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D019194:Ischemic Preconditioning / Q000379:methods; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
keywords: Extracellular vesicles; Hypoxia; Kidney ischemia-reperfusion injury; Remote ischemic preconditioning; Renal tubular epithelial cells