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[晚期糖基化终末产物受体RAGE/AGER:临床应用的综合观点]

[Receptor of advanced glycation endproducts RAGE/AGER: an integrative view for clinical applications].

作者信息

Barbezier Nicolas, Tessier Frédéric J, Chango Abalo

机构信息

Institut Polytechnique LaSalle Beauvais, Unité de recherche EGEAL UP:2012.10.101, Département des sciences de la nutrition et Santé, Beauvais, France.

出版信息

Ann Biol Clin (Paris). 2014 Nov-Dec;72(6):669-80. doi: 10.1684/abc.2014.1010.

Abstract

Advanced glycation endproducts or advanced glycation end products (AGEs) levels increase in blood or tissue during aging and in diseases such as diabetes and renal failure. The receptor of advanced glycation endproducts (RAGE), is a multi-ligand receptor belonging to the immunoglobulin superfamily. It is weakly expressed in most adult tissues. The link between the RAGE and its ligands triggers a cascade of intracellular events, followed by the transcription of a range of genes involved in different biological systems, as well as other reactions such as the formation of oxidative stress. All of these reactions lead to a series of functional changes that participate in neurological and vascular complications of diabetes, metabolic syndrome. They are also involved in Alzheimer's disease, arthritis, and some cancers. Besides the presence of these ligands, the chronic stimulation of the RAGE, or its isoforms trigger different signaling pathways and reactions. This makes complex the analysis of biological networks associated with multiple clinical traits. Many issues remain to be clarified in the pathogenicity of RAGE. In the era of the development of systems biology, integrative approach is expected allowing a better understanding of the overall effects of RAGE system. In this review, we discuss recent advances in our understanding of the biology of the RAGE, focusing on how systems biology influence our view it processes. The review should contribute to the better understanding of pathogenicity of "RAGE system" and to the transposition this new knowledge into clinical and translational research.

摘要

在衰老过程以及糖尿病和肾衰竭等疾病中,血液或组织中的晚期糖基化终产物(AGEs)水平会升高。晚期糖基化终产物受体(RAGE)是一种属于免疫球蛋白超家族的多配体受体。它在大多数成年组织中表达较弱。RAGE与其配体之间的联系会引发一系列细胞内事件,随后一系列参与不同生物系统的基因会转录,以及产生其他反应,如氧化应激的形成。所有这些反应都会导致一系列功能变化,这些变化参与糖尿病、代谢综合征的神经和血管并发症。它们还与阿尔茨海默病、关节炎和某些癌症有关。除了这些配体的存在,RAGE或其异构体受到的慢性刺激会触发不同的信号通路和反应。这使得与多种临床特征相关的生物网络分析变得复杂。在RAGE的致病性方面仍有许多问题有待阐明。在系统生物学发展的时代,期望采用综合方法能更好地理解RAGE系统的整体效应。在这篇综述中,我们讨论了我们对RAGE生物学理解的最新进展,重点关注系统生物学如何影响我们对其过程的看法。这篇综述应有助于更好地理解“RAGE系统”的致病性,并将这一新知识转化为临床和转化研究。

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