Development of an ELISA for esRAGE and its application to type 1 diabetic patients.
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 1 diabetic subjects without clinical nephropathy (urinary albumin excretion <300mg/g creatinine) and 55 healthy controls were analyzed by the ELISA. Circulating esRAGE concentrations in diabetic patients with simple and proliferative retinopathy (0.09+/-0.02ng/mL, n=16 and 0.08+/-0.02ng/mL, n=8, respectively) were significantly lower than in those without retinopathy (0.13+/-0.06ng/mL, n=23). The results indicate that esRAGE can be a useful biomarker to indicate individual variations in susceptibility to diabetic retinopathy.
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, Kanazawa 920-8640, Japan.
Shigeru
S
Sakurai
Yasuhiko
Y
Yamamoto
Hironori
H
Tamei
Hirokazu
H
Matsuki
Ken-Ichi
K
Obata
Li
L
Hui
Junnosuke
J
Miura
Mari
M
Osawa
Yasuko
Y
Uchigata
Yasuhiko
Y
Iwamoto
Takuo
T
Watanabe
Hideto
H
Yonekura
Hiroshi
H
Yamamoto
D000911:Antibodies, Monoclonal / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003930:Diabetic Retinopathy / Q000175:diagnosis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006801:Humans; D011379:Prognosis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012680:Sensitivity and Specificity; D012995:Solubility
D000911:Antibodies, Monoclonal; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic