title: Renalase contributes to the renal protection of delayed ischaemic preconditioning via the regulation of hypoxia-inducible factor-1α.
abstract: Ischaemic preconditioning (IPC) attenuates acute kidney injury (AKI) from renal ischaemia reperfusion. Renalase, an amine oxidase secreted by the proximal tubule, not only degrades circulating catecholamines but also protects against renal ischaemia reperfusion injury. Here, it has been suggested that the renoprotective effect of renal IPC is partly mediated by renalase. In a model of brief intermittent renal IPC, the increased cortex renalase expression was found to last for 48 hrs. IPC significantly reduced renal tubular inflammation, necrosis and oxidative stress following renal ischaemia reperfusion injury. Such effects were attenuated by blocking renalase with an anti-renalase monoclonal antibody. We further demonstrated that renalase expression was up-regulated by hypoxia in vitro via an hypoxia-inducible factor (HIF)-1α mechanism. The IPC-induced up-regulation of renalase in vivo was also reduced by pre-treatment with an HIF-1α inhibitor, 3-(5'-Hydroxymethyl-2'-furyl)-1-benzyl indazole. In summary, the renoprotective effect of IPC is partly dependent on the renalase expression, which may be triggered by hypoxia via an HIF-1α mechanism. Endogenous renalase shows potential as a therapeutic agent for the prevention and treatment of AKI.
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, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Guangyuan
authors.initials: G
authors.lastname: Zhang
authors.affiliation: St. Vincent's Hospital, Melbourne, VIC, Australia.
authors.forename: Tao
authors.initials: T
authors.lastname: Xing
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Zeyuan
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Urology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors.forename: Niansong
authors.initials: N
authors.lastname: Wang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015687:Cell Hypoxia; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D019194:Ischemic Preconditioning; D007668:Kidney / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D020011:Protective Agents / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020011:Protective Agents; D008995:Monoamine Oxidase; C521557:renalase
keywords: hypoxia-inducible factor; ischaemia/reperfusion injury; ischaemic preconditioning; renalase