TY - JOUR
T1 - Receptor for advanced glycation end products is a promising target of diabetic nephropathy
AU - Yamamoto, Yasuhiko
AU - Doi, Toshio
AU - Kato, Ichiro
AU - Shinohara, Harumichi
AU - Sakurai, Shigeru
AU - Yonekura, Hideto
AU - Watanabe, Takuo
AU - Myint, Kihn Mar
AU - Harashima, Ai
AU - Takeuchi, Masayoshi
AU - Takasawa, Shin
AU - Okamoto, Hiroshi
AU - Hashimoto, Noriyoshi
AU - Asano, Masahide
AU - Yamamoto, Hiroshi
PY - 2005
Y1 - 2005
N2 - Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) interactions have been implicated in the development of diabetic vascular complications, which cause various disabilities and shortened life expectancy, and reduced quality of life in patients with diabetes. Diabetes-induced RAGE-overexpressing transgenic mice exhibited the exacerbation of the indices of nephropathy, and this was prevented by the inhibition of AGE formation. We also created RAGE-deficient mice by homologous recombination. They showed marked amelioration of diabetic nephropathy as compared with wild-type mice. Through an analysis of vascular polysomal poly(A)+ RNA, we identified a novel splice variant coding for a soluble RAGE protein and named it endogenous secretory RAGE (esRAGE). esRAGE was able to protect AGE-induced vascular cell injuries as a decoy receptor and was actually detected in human circulation. We conclude that RAGE plays an active role in the development of diabetic vascular complications, especially nephropathy, and is a promising target for overcoming this disease. The esRAGE, an endogenous decoy receptor, may be related to individual variations in resistance to the development of diabetic vascular complications.
AB - Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) interactions have been implicated in the development of diabetic vascular complications, which cause various disabilities and shortened life expectancy, and reduced quality of life in patients with diabetes. Diabetes-induced RAGE-overexpressing transgenic mice exhibited the exacerbation of the indices of nephropathy, and this was prevented by the inhibition of AGE formation. We also created RAGE-deficient mice by homologous recombination. They showed marked amelioration of diabetic nephropathy as compared with wild-type mice. Through an analysis of vascular polysomal poly(A)+ RNA, we identified a novel splice variant coding for a soluble RAGE protein and named it endogenous secretory RAGE (esRAGE). esRAGE was able to protect AGE-induced vascular cell injuries as a decoy receptor and was actually detected in human circulation. We conclude that RAGE plays an active role in the development of diabetic vascular complications, especially nephropathy, and is a promising target for overcoming this disease. The esRAGE, an endogenous decoy receptor, may be related to individual variations in resistance to the development of diabetic vascular complications.
KW - AGE
KW - Diabetic nephropathy
KW - RAGE
KW - esRAGE
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U2 - 10.1196/annals.1333.064
DO - 10.1196/annals.1333.064
M3 - Article
C2 - 16037279
AN - SCOPUS:23744458810
VL - 1043
SP - 562
EP - 566
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
SN - 0077-8923
ER -
