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DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy

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 C57...

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Autores principales: Kaida, Yusuke, Fukami, Kei, Matsui, Takanori, Higashimoto, Yuichiro, Nishino, Yuri, Obara, Nana, Nakayama, Yosuke, Ando, Ryotaro, Toyonaga, Maki, Ueda, Seiji, Takeuchi, Masayoshi, Inoue, Hiroyoshi, Okuda, Seiya, Yamagishi, Sho-ichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749365/
https://www.ncbi.nlm.nih.gov/pubmed/23630304
http://dx.doi.org/10.2337/db12-1608
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author Kaida, Yusuke
Fukami, Kei
Matsui, Takanori
Higashimoto, Yuichiro
Nishino, Yuri
Obara, Nana
Nakayama, Yosuke
Ando, Ryotaro
Toyonaga, Maki
Ueda, Seiji
Takeuchi, Masayoshi
Inoue, Hiroyoshi
Okuda, Seiya
Yamagishi, Sho-ichi
author_facet Kaida, Yusuke
Fukami, Kei
Matsui, Takanori
Higashimoto, Yuichiro
Nishino, Yuri
Obara, Nana
Nakayama, Yosuke
Ando, Ryotaro
Toyonaga, Maki
Ueda, Seiji
Takeuchi, Masayoshi
Inoue, Hiroyoshi
Okuda, Seiya
Yamagishi, Sho-ichi
author_sort Kaida, Yusuke
collection PubMed
description 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.
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spelling pubmed-37493652014-09-01 DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy Kaida, Yusuke Fukami, Kei Matsui, Takanori Higashimoto, Yuichiro Nishino, Yuri Obara, Nana Nakayama, Yosuke Ando, Ryotaro Toyonaga, Maki Ueda, Seiji Takeuchi, Masayoshi Inoue, Hiroyoshi Okuda, Seiya Yamagishi, Sho-ichi Diabetes Original Research 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. American Diabetes Association 2013-09 2013-08-15 /pmc/articles/PMC3749365/ /pubmed/23630304 http://dx.doi.org/10.2337/db12-1608 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Kaida, Yusuke
Fukami, Kei
Matsui, Takanori
Higashimoto, Yuichiro
Nishino, Yuri
Obara, Nana
Nakayama, Yosuke
Ando, Ryotaro
Toyonaga, Maki
Ueda, Seiji
Takeuchi, Masayoshi
Inoue, Hiroyoshi
Okuda, Seiya
Yamagishi, Sho-ichi
DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy
title DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy
title_full DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy
title_fullStr DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy
title_full_unstemmed DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy
title_short DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy
title_sort dna aptamer raised against ages blocks the progression of experimental diabetic nephropathy
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3749365/
https://www.ncbi.nlm.nih.gov/pubmed/23630304
http://dx.doi.org/10.2337/db12-1608
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