title: DNA aptamer raised against AGEs blocks the progression of experimental diabetic nephropathy.
abstract: Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We screened DNA aptamer directed against AGEs (AGEs-aptamer) in vitro and examined its effects on renal injury in KKAy/Ta mice, an animal model of type 2 diabetes. Eight-week-old male KKAy/Ta or C57BL/6J mice received continuous intraperitoneal infusion of AGEs- or control-aptamer for 8 weeks. AGEs-aptamer was detected and its level was increased in the kidney for at least 7 days. The elimination half-lives of AGEs-aptamer in the kidney were about 7 days. Compared with those in C57BL/6J mice, glomerular AGEs levels were significantly increased in KKAy/Ta mice, which were blocked by AGEs-aptamer. Urinary albumin and 8-hydroxy-2'-deoxy-guanosine levels were increased, and glomerular hypertrophy and enhanced extracellular matrix accumulation were observed in KKAy/Ta mice, all of which were prevented by AGEs-aptamer. Moreover, AGEs-aptamer significantly reduced gene expression of RAGE, monocyte chemoattractant protein-1, connective tissue growth factor, and type IV collagen both in the kidney of KKAy/Ta mice and in AGE-exposed human cultured mesangial cells. Our present data suggest that continuous administration of AGEs-aptamer could protect against experimental diabetic nephropathy by blocking the AGEs-RAGE axis and may be a feasible and promising therapeutic strategy for the treatment of diabetic nephropathy.
authors: Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors: Yusuke
authors: Y
authors: Kaida
authors: Kei
authors: K
authors: Fukami
authors: Takanori
authors: T
authors: Matsui
authors: Yuichiro
authors: Y
authors: Higashimoto
authors: Yuri
authors: Y
authors: Nishino
authors: Nana
authors: N
authors: Obara
authors: Yosuke
authors: Y
authors: Nakayama
authors: Ryotaro
authors: R
authors: Ando
authors: Maki
authors: M
authors: Toyonaga
authors: Seiji
authors: S
authors: Ueda
authors: Masayoshi
authors: M
authors: Takeuchi
authors: Hiroyoshi
authors: H
authors: Inoue
authors: Seiya
authors: S
authors: Okuda
authors: Sho-ichi
authors: S
authors: Yamagishi
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D052157:Aptamers, Nucleotide; D017127:Glycation End Products, Advanced
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