Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase

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...

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Main Authors:	Wang, Feng, Yin, Jianyong, Lu, Zeyuan, Zhang, Guangyuan, Li, Junhui, Xing, Tao, Zhuang, Shougang, Wang, Niansong
Format:	Online
Language:	English
Published:	Elsevier 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972520/

id	pubmed-4972520
recordtype	oai_dc
spelling	pubmed-49725202016-08-10 Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase Wang, Feng Yin, Jianyong Lu, Zeyuan Zhang, Guangyuan Li, Junhui Xing, Tao Zhuang, Shougang Wang, Niansong Research Paper 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 24 h 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 TNFα levels in the muscle and blood, and up-regulated renalase and phosphorylated IκBα expression in the kidney. Pretreatment with TNFα antagonist or NF-κB inhibitor, largely blocked renalase expression. Besides, TNFα 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 TNFα/NF-κB pathway. Elsevier 2016-05-18 /pmc/articles/PMC4972520/ /pubmed/27333047 http://dx.doi.org/10.1016/j.ebiom.2016.05.017 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wang, Feng Yin, Jianyong Lu, Zeyuan Zhang, Guangyuan Li, Junhui Xing, Tao Zhuang, Shougang Wang, Niansong
spellingShingle	Wang, Feng Yin, Jianyong Lu, Zeyuan Zhang, Guangyuan Li, Junhui Xing, Tao Zhuang, Shougang Wang, Niansong Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase
author_facet	Wang, Feng Yin, Jianyong Lu, Zeyuan Zhang, Guangyuan Li, Junhui Xing, Tao Zhuang, Shougang Wang, Niansong
author_sort	Wang, Feng
title	Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase
title_short	Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase
title_full	Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase
title_fullStr	Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase
title_full_unstemmed	Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase
title_sort	limb ischemic preconditioning protects against contrast-induced nephropathy via renalase
description	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 24 h 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 TNFα levels in the muscle and blood, and up-regulated renalase and phosphorylated IκBα expression in the kidney. Pretreatment with TNFα antagonist or NF-κB inhibitor, largely blocked renalase expression. Besides, TNFα 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 TNFα/NF-κB pathway.
publisher	Elsevier
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972520/
_version_	1613620825019121664

Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase

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