title: 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 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.
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: zyzwq1030@hotmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Zeyuan
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing 210009, China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Li
authors.affiliation: St. Vincent's Hospital, Fitzroy, Melbourne, VIC, Australia.
authors.forename: Tao
authors.initials: T
authors.lastname: Xing
authors.affiliation: Department of Medicine, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island, USA. Electronic address: szhuang@lifespan.org.
authors.forename: Shougang
authors.initials: S
authors.lastname: Zhuang
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: wangniansong2008@163.com.
authors.forename: Niansong
authors.initials: N
authors.lastname: Wang
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D019194:Ischemic Preconditioning; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008995:Monoamine Oxidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D020011:Protective Agents; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D008995:Monoamine Oxidase; C521557:renalase; D053148:Caspase 3
keywords: Contrast induced nephropathy; Limb ischemic preconditioning; Renalase; TNFα