title: Extracellular renalase protects cells and organs by outside-in signalling.
abstract: Renalase was discovered as a protein synthesized by the kidney and secreted in blood where it circulates at a concentration of approximately 3-5 μg/ml. Initial reports suggested that it functioned as an NAD(P)H oxidase and could oxidize catecholamines. Administration of renalase lowers blood pressure and heart rate and also protects cells and organs against ischaemic and toxic injury. Although renalase's protective effect was initially ascribed to its oxidase properties, a paradigm shift in our understanding of the cellular actions of renalase is underway. We now understand that, independent of its enzymatic properties, renalase functions as a cytokine that provides protection to cells, tissues and organs by interacting with its receptor to activate protein kinase B, JAK/STAT, and the mitogen-activated protein kinase pathways. In addition, recent studies suggest that dysregulated renalase signalling may promote survival of several tumour cells due to its capacity to augment expression of growth-related genes. In this review, we focus on the cytoprotective actions of renalase and its capacity to sustain cancer cell growth and also the translational opportunities these findings represent for the development of novel therapeutic strategies for organ injury and cancer.
authors.affiliation: Department of Medicine, Veterans Affairs Connecticut Healthcare System, Yale University, New Haven, CT, USA.|Department of Cardiology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicine, Veterans Affairs Connecticut Healthcare System, Yale University, New Haven, CT, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Safirstein
authors.affiliation: Department of Medicine, Veterans Affairs Connecticut Healthcare System, Yale University, New Haven, CT, USA.
authors.forename: Heino
authors.initials: H
authors.lastname: Velazquez
authors.affiliation: Department of Medicine, Veterans Affairs Connecticut Healthcare System, Yale University, New Haven, CT, USA.
authors.forename: Xiao-Jia
authors.initials: XJ
authors.lastname: Guo
authors.affiliation: Department of Medicine, Veterans Affairs Connecticut Healthcare System, Yale University, New Haven, CT, USA.|Department of Surgery, University of Connecticut, Farmington, CT, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Hollander
authors.affiliation: Department of Medicine, Veterans Affairs Connecticut Healthcare System, Yale University, New Haven, CT, USA.
authors.forename: John
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Medicine, Veterans Affairs Connecticut Healthcare System, Yale University, New Haven, CT, USA.
authors.forename: Tian-Min
authors.initials: TM
authors.lastname: Chen
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Mu
authors.affiliation: Department of Medicine, Veterans Affairs Connecticut Healthcare System, Yale University, New Haven, CT, USA.
authors.forename: Gary V
authors.initials: GV
authors.lastname: Desir
mesh_terms: D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008995:Monoamine Oxidase / Q000378:metabolism* / Q000627:therapeutic use; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D010084:Oxidation-Reduction
chemical_list: D002395:Catecholamines; D016207:Cytokines; D008995:Monoamine Oxidase; C521557:renalase; D019255:NADPH Oxidases
keywords: cell signalling; immune-oncology; ischaemic injury; macrophages; renalase; survival factor