Steenbeke Mieke, De Bruyne Sander, De Buyzere Marc, Lapauw Bruno, Speeckaert Reinhart, Petrovic Mirko, Delanghe Joris R, Speeckaert Marijn M
Department of Nephrology, Ghent University Hospital, Ghent, Belgium.
Department of Clinical Chemistry, Ghent University Hospital, Ghent, Belgium.
Crit Rev Clin Lab Sci. 2021 Mar;58(2):113-130. doi: 10.1080/10408363.2020.1791045. Epub 2020 Jul 15.
Isoforms of the receptor for advanced glycation end-product (RAGE) protein, which lack the transmembrane and the signaling (soluble RAGE or sRAGE) domains are hypothesized to counteract the detrimental action of the full-length receptor by acting as a decoy, and they provide a potential tool to treat RAGE-associated diseases. Multiple studies have explored the relationship between sRAGE and endogenous secretory RAGE and its polymorphism and obesity, metabolic syndrome, atherosclerosis, kidney function, and increased mortality in the general population. In addition, sRAGE may be a key player in the pathogenesis of diabetes mellitus and its microvascular (e.g. kidney disease) as well as macrovascular (e.g. cardiovascular disease) complications. In this review, we focus on the role of sRAGE as a biomarker in these specific areas. As there is a lack of an underlying unifying hypothesis about how sRAGE changes according to the disease condition or risk factor, there is a call to incorporate all three players of the AGE-RAGE axis into a new universal biomarker/risk marker: (AGE + RAGE)/sRAGE. However, the measurement of RAGE in humans is not practical as it is a cell-bound receptor for which tissue is required for analysis. A high AGE/sRAGE ratio may be a valuable alternative and practical universal biomarker/risk marker for diseases associated with the AGE-RAGE axis, irrespective of low or high serum sRAGE concentrations.
晚期糖基化终末产物受体（RAGE）蛋白的异构体缺乏跨膜和信号传导（可溶性RAGE或sRAGE）结构域，据推测它们可作为诱饵来抵消全长受体的有害作用，并且为治疗与RAGE相关的疾病提供了一种潜在工具。多项研究探讨了sRAGE与内源性分泌型RAGE之间的关系及其多态性与肥胖、代谢综合征、动脉粥样硬化、肾功能以及普通人群死亡率增加之间的关系。此外，sRAGE可能是糖尿病及其微血管并发症（如肾病）以及大血管并发症（如心血管疾病）发病机制中的关键因素。在本综述中，我们重点关注sRAGE作为生物标志物在这些特定领域中的作用。由于缺乏关于sRAGE如何根据疾病状况或风险因素而变化的潜在统一假说，因此有人呼吁将AGE-RAGE轴的所有三个因素纳入一个新的通用生物标志物/风险标志物：（AGE + RAGE）/sRAGE。然而，在人体中测量RAGE并不实际，因为它是一种细胞结合受体，需要组织进行分析。无论血清sRAGE浓度是低还是高，高AGE/sRAGE比值可能是与AGE-RAGE轴相关疾病的一种有价值的替代且实用的通用生物标志物/风险标志物。
