title: Receptor for advanced glycation end products is a promising target of diabetic nephropathy.
abstract: 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.
authors.affiliation: 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
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Doi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kato
authors.forename: Harumichi
authors.initials: H
authors.lastname: Shinohara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sakurai
authors.forename: Hideto
authors.initials: H
authors.lastname: Yonekura
authors.forename: Takuo
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kihn Mar
authors.initials: KM
authors.lastname: Myint
authors.forename: Ai
authors.initials: A
authors.lastname: Harashima
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Shin
authors.initials: S
authors.lastname: Takasawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okamoto
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamamoto
mesh_terms: 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*
chemical_list: 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