Receptor for advanced glycation end products is a promising target of diabetic nephropathy.
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.
Yamamoto
Yasuhiko
Y
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan. yamamoto@med.kanazawa-u.ac.jp
Doi
Toshio
T
Kato
Ichiro
I
Shinohara
Harumichi
H
Sakurai
Shigeru
S
Yonekura
Hideto
H
Watanabe
Takuo
T
Myint
Kihn Mar
KM
Harashima
Ai
A
Takeuchi
Masayoshi
M
Takasawa
Shin
S
Okamoto
Hiroshi
H
Hashimoto
Noriyoshi
N
Asano
Masahide
M
Yamamoto
Hiroshi
H
D000818:Animals; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse