Abstract

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.

摘要

假设缺乏跨膜和信号（可溶性 RAGE 或 sRAGE）结构域的晚期糖基化终产物 (RAGE) 蛋白受体的同种型通过充当诱饵来抵消全长受体的有害作用，并且它们提供治疗 RAGE 相关疾病的潜在工具。多项研究探讨了 sRAGE 与内源性分泌性 RAGE 及其多态性与肥胖、代谢综合征、动脉粥样硬化、肾功能和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（例如肾脏疾病）以及大血管（例如心血管疾病）并发症的发病机制的关键参与者。在这篇综述中，我们关注 sRAGE 作为这些特定领域的生物标志物的作用。由于缺乏关于 sRAGE 如何根据疾病状况或风险因素变化的潜在统一假设，因此呼吁将 AGE-RAGE 轴的所有三个参与者纳入新的通用生物标志物/风险标志物：（AGE + RAGE)/sRAGE。然而，在人类中测量 RAGE 是不切实际的，因为它是一种细胞结合受体，需要对其进行组织分析。高 AGE/sRAGE 比率可能是与 AGE-RAGE 轴相关疾病的有价值的替代和实用的通用生物标志物/风险标志物，无论血清 sRAGE 浓度是低还是高。在人体中测量 RAGE 是不切实际的，因为它是一种细胞结合受体，需要对其进行组织分析。高 AGE/sRAGE 比率可能是与 AGE-RAGE 轴相关疾病的有价值的替代和实用的通用生物标志物/风险标志物，无论血清 sRAGE 浓度是低还是高。在人体中测量 RAGE 是不切实际的，因为它是一种细胞结合受体，需要对其进行组织分析。高 AGE/sRAGE 比率可能是与 AGE-RAGE 轴相关疾病的有价值的替代和实用的通用生物标志物/风险标志物，无论血清 sRAGE 浓度是低还是高。