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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2013
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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. |
format | Online Article Text |
id | pubmed-3749365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
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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