Development of an ELISA for esRAGE and its application to type 1 diabetic patients

Development of an ELISA for esRAGE and its application to type 1 diabetic patients
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DOI:
10.1016/j.diabres.2005.12.013
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发表时间:
2006-08-01
影响因子:
5.1
通讯作者:
Yamamoto, Hiroshi
Yamamoto, Hiroshi
中科院分区:
医学3区
文献类型:
--
作者:
Sakurai, Shigeru;Yamamoto, Yasuhiko;Yamamoto, Hiroshi

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我们最近在培养的人血管细胞中发现了一种天然存在的可溶性RAGE(晚期糖基化终产物受体,AGE受体),并将其命名为内源性分泌型RAGE(EsRAGE)。EsRAGE是通过选择性RNA剪接产生的,能够捕获AGE,并对AGE诱导的内皮细胞损伤起到保护作用。在本研究中,首次证实了esRAGE在人体循环中的存在,并建立了一种高度敏感和特异的esRAGE夹心ELISA法,以确定esRAGE是否与个体对糖尿病血管并发症发生的抵抗有关。用双抗体夹心法检测了47例无临床肾病(尿白蛋白排泄量为300 mg/g肌酐)的I型糖尿病患者和55例健康人的血清。单纯视网膜病变组和增殖性视网膜病变组的血浆esRAGE浓度分别为0.09+/-0.02 ng/mL(n=16)和0.08+/-0.02 ng/m L(n=8),明显低于无视网膜病变组(0.13+/-0.06 ng/m L,n=23)。结果表明,esRAGE可作为一种有用的生物标记物来指示糖尿病视网膜病变易感性的个体差异。(C)2006年,爱思唯尔爱尔兰有限公司出版。
We recently identified a naturally occurring soluble form of RAGE (the receptor for advanced glycation endproducts, receptor for AGE) in cultured human vascular cells, and named it endogenous secretory RAGE (esRAGE). esRAGE is generated by alternative RNA splicing and is able to capture AGE, and exerts protection against AGE-induced endothelial cell injury. In the present study, the presence of esRAGE in human circulation was demonstrated for the first time, and a highly sensitive and specific sandwich ELISA system for esRAGE was developed to see whether esRAGE could be related to an individual resistance to the development of diabetic vascular complications. Sera from 47 type I diabetic subjects without clinical nephropathy (urinary albumin excretion < 300 mg/g creatinine) and 55 healthy controls were analyzed by the ELISA. Circulating esRAGE concentrations in diabetic patients with simple and proliferative retinopathy (0.09 +/- 0.02 ng/mL, n = 16 and 0.08 +/- 0.02 ng/mL, n = 8, respectively) were significantly lower than in those without retinopathy (0.13 +/- 0.06 ng/mL, n = 23). The results indicate that esRAGE can be a useful biomarker to indicate individual variations in susceptibility to diabetic retinopathy. (c) 2006 Published by Elsevier Ireland Ltd.