Hiroshi Yamamoto, Takuo Watanabe, Yasuhiko Yamamoto, Hideto Yonekura, Seiichi Munesue, Ai Harashima, Kazuyo Ooe, Sharmin Hossain, Hidehito Saito and Naho Murakami Pages 752 - 757 ( 6 )
As is diabetes itself, diabetic angiopathy is a multi-factorial disease. Advanced glycation endproducts (AGE) cause vascular cell derangement characteristic of diabetes, and this is mainly mediated by their interaction with receptor for AGE (RAGE). When made diabetic, RAGE-overexpressing transgenic mice exhibited exacerbation of the indices of nephropathy, and this was prevented by the inhibition of AGE formation. On the other hand, RAGE-deficient animals showed amelioration of diabetic nephropathy. Accordingly, AGE and RAGE should be regarded as environmental and cellular accounts and as a potential therapeutic target for diabetic nephropathy. In effect, substances that inhibit the formation of AGE, break preformed AGE, change metabolic flows away from glycation, antagonize RAGE, and capture RAGE ligands have been proven as effective remedies against this life-threatening disease.
iNOS transgenic mice, endothelial cells, aminoguanidine, RAGE gene, diabetic nephropathy
Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8640, Japan.