RAGE Control of Diabetic Nephropathy in a Mouse Model

• DOI: 10.2337/db06-0221
• Publication Date: 2006-08-25T21:48:55Z
• Authors: Khin-Mar Myint; Yasuhiko Yamamoto; Toshio Doi; Ichiro Kato; Ai Harashima; Hideto Yonekura; Takuo Watanabe; Harumichi Shinohara; Masayoshi Takeuchi; Koichi Tsuneyama; Noriyoshi Hashimoto; Masahide Asano; Shin Takasawa; Hiroshi Okamoto; Hiroshi Yamamoto
• Keywords: Albuminuria; RAGE; Glomerulosclerosis

Diabetic nephropathy is a major microvascular complication in long-standing diabetic patients who eventually undergo renal dialysis or transplantation. To prevent development of this disease and to improve advanced kidney injury, effective therapies directed toward the key molecular target are required. In study, we examined whether inhibition receptor for glycation end products (RAGE) could attenuate changes kidney. Here, show that inactivation RAGE gene mouse model results significant suppression changes, including enlargement, increased glomerular cell number, mesangial expansion, glomerulosclerosis, albuminuria, serum creatinine compared with wild-type mice. The degree injury was proportional dosage. Furthermore, low-molecular weight heparin (LMWH) can bind at mean equilibrium dissociation constant (K(d)) value approximately 17 nmol/l act as an antagonist RAGE. LMWH treatment mice significantly prevented albuminuria glomerulosclerosis dose-dependent manner; it also improved indexes advanced-stage nephropathy. This study provides insight into pathological role both early- advanced-phase suggests antagonists will be useful remedy