Open AccessRenalase contributes to the renal protection of delayed ischaemic preconditioning via the regulation of hypoxia‐inducible factor‐1α
Author(s) -
Wang Feng,
Zhang Guangyuan,
Xing Tao,
Lu Zeyuan,
Li Junhui,
Peng Cheng,
Liu Guohua,
Wang Niansong
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12527
Subject(s) - hypoxia (environmental) , ischemia , kidney , oxidative stress , endogeny , ischemic preconditioning , renal ischemia , acute kidney injury , medicine , pharmacology , reperfusion injury , renal cortex , inflammation , endocrinology , chemistry , oxygen , organic chemistry
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 .