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Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase.


ABSTRACT: Clinical trials shows that remote ischemic preconditioning (IPC) can protect against contrast induced nephropathy (CIN) in risky patients, however, the exact mechanism is unclear. In this study, we explored whether renalase, an amine oxidase that has been previously shown to mediate reno-protection by local IPC, would also mediate the same effect elicited by remote IPC in animal model. Limb IPC was performed for 24h followed by induction of CIN. Our results indicated that limb IPC prevented renal function decline, attenuated tubular damage and reduced oxidative stress and inflammation in the kidney. All those beneficial effects were abolished by silencing of renalase with siRNA. This suggests that similar to local IPC, renalase is also critically involved in limb IPC-elicited reno-protection. Mechanistic studies showed that limb IPC increased TNF? levels in the muscle and blood, and up-regulated renalase and phosphorylated I?B? expression in the kidney. Pretreatment with TNF? antagonist or NF-?B inhibitor, largely blocked renalase expression. Besides, TNF? preconditioning increased expression of renal renalase in vivo and in vitro, and attenuated H2O2 induced apoptosis in renal tubular cells. Collectively, our results suggest that limb IPC-induced reno-protection in CIN is dependent on increased renalase expression via activation of the TNF?/NF-?B pathway.

SUBMITTER: Wang F 

PROVIDER: S-EPMC4972520 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase.

Wang Feng F   Yin Jianyong J   Lu Zeyuan Z   Zhang Guangyuan G   Li Junhui J   Xing Tao T   Zhuang Shougang S   Wang Niansong N  

EBioMedicine 20160518


Clinical trials shows that remote ischemic preconditioning (IPC) can protect against contrast induced nephropathy (CIN) in risky patients, however, the exact mechanism is unclear. In this study, we explored whether renalase, an amine oxidase that has been previously shown to mediate reno-protection by local IPC, would also mediate the same effect elicited by remote IPC in animal model. Limb IPC was performed for 24h followed by induction of CIN. Our results indicated that limb IPC prevented rena  ...[more]

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