Open AccessExtracellular renalase protects cells and organs by outside‐in signalling
Author(s) -
Wang Yang,
Safirstein Robert,
Velazquez Heino,
Guo XiaoJia,
Hollander Lindsay,
Chang John,
Chen TianMin,
Mu JianJun,
Desir Gary V.
Publication year - 2017
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.13062
Subject(s) - kinase , nad+ kinase , microbiology and biotechnology , extracellular , protein kinase a , biology , signal transduction , receptor , cancer cell , cancer research , enzyme , cancer , medicine , biochemistry
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.