Guo Xiaojia, Wang Ling, Velazquez Heino, Safirstein Robert, Desir Gary V
aDepartment of Medicine, VACHS, Yale University, New Haven, Connecticut, USA bRenal Division, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Curr Opin Nephrol Hypertens. 2014 Sep;23(5):513-8. doi: 10.1097/MNH.0000000000000044.
Remarkable progress has been achieved over the past 2 years in understanding the cellular actions of renalase, its pathophysiology and potential therapeutic utility.
There has been a paradigm shift in our thinking about the mechanisms underlying the cellular actions of renalase. We now understand that, independent of its enzymatic properties, renalase functions as a signaling molecule, a cytokine that interacts with a yet-to-be identified plasma membrane receptor(s) to activate protein kinase B and the mitogen-activated protein kinase pathway. These signaling properties are critical to its cytoprotective effects. New information regarding renalase's enzymatic function as an α-nicotinamide adenine dinucleotide oxidase/anomerase will be reviewed. Lastly, we will discuss the association of certain single nucleotide polymorphisms in the renalase gene with type 1 diabetes and with ischemic stroke, and the clinical implications of these findings.
The consistent association of renalase single nucleotide polymorphisms and the development of type 1 diabetes is a great interest particularly because we now understand that renalase functions as a cytokine. Future work on renalase should focus on exploring the identity of its receptor(s), and its potential role as an immune modulator.
在过去两年中,我们对肾酶的细胞作用、病理生理学及潜在治疗用途的理解取得了显著进展。
我们对肾酶细胞作用机制的认识发生了范式转变。现在我们知道,肾酶独立于其酶特性,作为一种信号分子发挥作用,它是一种细胞因子,可与尚未确定的质膜受体相互作用,激活蛋白激酶B和丝裂原活化蛋白激酶途径。这些信号特性对其细胞保护作用至关重要。本文将综述有关肾酶作为α-烟酰胺腺嘌呤二核苷酸氧化酶/异构酶的酶功能的新信息。最后,我们将讨论肾酶基因中某些单核苷酸多态性与1型糖尿病和缺血性中风的关联以及这些发现的临床意义。
肾酶单核苷酸多态性与1型糖尿病发生之间的持续关联尤其令人关注,因为我们现在知道肾酶作为一种细胞因子发挥作用。未来关于肾酶的研究应集中于探索其受体的身份及其作为免疫调节剂的潜在作用。