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Receptor for Advanced Glycation End Products Is a Promising Target of Diabetic Nephropathy
Author(s) -
YAMAMOTO YASUHIKO,
DOI TOSHIO,
KATO ICHIRO,
SHINOHARA HARUMICHI,
SAKURAI SHIGERU,
YONEKURA HIDETO,
WATANABE TAKUO,
MYINT KIHN MAR,
HARASHIMA AI,
TAKEUCHI MASAYOSHI,
TAKASAWA SHIN,
OKAMOTO HIROSHI,
HASHIMOTO NORIYOSHI,
ASANO MASAHIDE,
YAMAMOTO HIROSHI
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1333.064
Subject(s) - rage (emotion) , glycation , diabetic nephropathy , medicine , receptor , diabetes mellitus , advanced glycation end product , decoy , nephropathy , endocrinology , immunology , biology , neuroscience
A bstract : 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.