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Novel therapeutic approach against receptor for advanced glycation end products in patients with diabetic nephropathy or RPGN.

Research Project

Project/Area Number 22590904
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionKurume University

Principal Investigator

FUKAMI Kei  久留米大学, 医学部, 准教授 (80309781)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsdiabetic nephropathy / RPGN / glycation / RAGE / AGEs / aptamer / 糖尿病性腎症 / アプタマー / Diabetic Nephropathy
Research Abstract

Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We examined effects of AGE- and RAGE-aptamer on renal injury in KKAy/Ta 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 extracellular matrix accumulation were prevented by AGEs-aptamer. Our present data suggest that continuous administration of AGEs-aptamer may be a feasible and promising therapeutic strategy for the treatment of diabeticnephropathy.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (56 results)

All 2013 2012 2011 2010

All Journal Article (28 results) (of which Peer Reviewed: 28 results) Presentation (10 results) Book (16 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Telmisartan inhibits AGE-induced podocyte damage and detachment.2013

    • Author(s)
      Fukami K,Yamagishi S, Kaifu K, Matsui T, Kaida Y, Ueda S, Takeuchi M, Asanuma K, Okuda S.
    • Journal Title

      Microvasc Res.

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA aptamer raised against AGEs blocks the progression of experimental diabetic nephropathy.2013

    • Author(s)
      Kaida Y, Fukami K, Matsui T, Higashimoto Y, Nishino Y, Obara N, Nakayama Y, Ando R, Toyonaga M, Ueda S, Takeuchi M, Inoue, H, Okuda S, Yamagishi
    • Journal Title

      Diabetes(S. Kaida Y and Fukami K contributed equally to this study)

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evidence for a positive association between serum carnitine and free testosterone levels in uremic men with hemodialysis.2013

    • Author(s)
      Sakai K, Fukami K, Yamagishi S, Kaida Y, Adachi T, Ando R, Manabe R, Otsuka A, Sugi K, Ueda S and Okuda S.
    • Journal Title

      Rejevenation Res.

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] AGEs-RAGE system in cardiovasculardisease.2013

    • Author(s)
      Fukami K, Yamagishi S, Okuda S.
    • Journal Title

      Cur Pharm Des

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Switching from Calcium Carbonate to Lanthanum Carbonate on Bone Mineral Metabolism in Hemodialysis Patients.2013

    • Author(s)
      Manabe R, Fukami K, Ando R, Sakai K, Kusumoto T, Hazama H, Adachi T, Kaida K, Nakayama N, Ueda S, Kohno K, Wada Y, Yamagishi S, Okuda S.
    • Journal Title

      Ther Apher Dial. 17Suppl

      Volume: 1 Pages: 35-40

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] First reported case of collagenofibrotic glomerulopathy with a full-house pattern of immune deposits.2013

    • Author(s)
      Fukami K, Yamagishi S, Minezaki TNishi S, Hisano S, Okuda S.
    • Journal Title

      Clin Nephrol.

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glucagon-like Peptide-1 Receptor Agonist Inhibits Asymmetric Dimethylarginine Generation in the Kidney of Streptozotocin-Induced Diabetic Rats by Blocking Advanced Glycation End Product-Induced Protein Arginine Methyltranferase-1 Expression.2013

    • Author(s)
      Ojima A, Ishibashi Y, Matsui T, Maeda S, Nishino Y, Takeuchi M, Fukami K, Yamagishi SI. Am J Pathol.
    • Journal Title

      Am J Pathol.

      Volume: 182(1) Pages: 132-41

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serum asymmetric dimethylarginine levels are independently associated with procollagen III N-terminal peptide in non-alcoholic fatty liver disease patients.2013

    • Author(s)
      Hyogo H, Yamagishi S, Maeda S, Fukami K, Ueda S, Okuda S, Nakahara T, Kimura Y, Ishitobi T, Kazuki C.
    • Journal Title

      Clin Exp Med.

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] PEDF inhibits AGE-induced podocyte apoptosis via PPAR-gamma activation.2013

    • Author(s)
      Ishibashi Y, Matsui T, Ohta K, Tanoue R, Takeuchi M, Asanuma K, Fukami K, Okuda S, Nakamura K, Yamagishi S.
    • Journal Title

      Microvasc Res

      Volume: (85) Pages: 54-8

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Experimentaldiabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice.2013

    • Author(s)
      Takamiya Y, Fukami K, Yamagishi S, Kaida Y, Nakayama Y, Obara N, Iwatani R, Ando R, Koike K, Matsui M, Nishino Y, Ueda S, Cooper ME, and Okuda S.
    • Journal Title

      Nephrol Dial Transplant.

      Volume: 28(1) Pages: 55-62

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Switching from Calcium Carbonate to Lanthanum Carbonate on Bone Mineral Metabolism in Hemodialysis Patients.2013

    • Author(s)
      Manabe S
    • Journal Title

      Ther Apher Dial

      Volume: 17Suppl Issue: S1 Pages: 35-40

    • DOI

      10.1111/1744-9987.12037

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glucagon-like peptide-1 receptor agonist inhibits asymmetric dimethylarginine generation in the kidney of streptozotocin-induced diabetic rats by blocking advanced glycation end product-induced protein arginine methyltranferase-1 expression.2013

    • Author(s)
      Ayako Ojima
    • Journal Title

      Am. J. Pathol.

      Volume: 182 Issue: 1 Pages: 132-141

    • DOI

      10.1016/j.ajpath.2012.09.016

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Experimental diabetic nephropathy is accelerated in matrix metalloproteinase-2 knockout mice.2013

    • Author(s)
      Takamiya Y
    • Journal Title

      Nephrol Dial Transplant

      Volume: 28 Issue: 1 Pages: 55-62

    • DOI

      10.1093/ndt/gfs387

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in hemodialysis patients.2012

    • Author(s)
      Adachi T, Fukami K, Yamagishi S, Kaida Y, Ando R, Sakai K, Adachi H
    • Journal Title

      Otsuka A, Ueda S, Sugi Kand Okuda S. Nephrology

      Volume: 17(8) Pages: 689-94

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Proteinuria elevates asymmetric dimethylarginine levels via protein arginine methyltransferase-1 overexpression in a rat model of nephrotic syndrome.2012

    • Author(s)
      Kaida Y, Ueda S, Yamagishi S, Nakayama Y, Ando R, Iwatani R, Fukami K, Okuda S.
    • Journal Title

      Life sciences

      Volume: 24(91) Pages: 301-305

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Role of advanced glycation end products (AGEs) oxidative stress in vascular complications in diabetes.2012

    • Author(s)
      Yamagishi SI, Maeda S, Matsui T, Ueda S, Fukami K, Okuda S.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1820(5) Pages: 663-671

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Decreased serum carnitine is independently correlated with increased tissue accumulation levels of advanced glycation end products in hemodialysis patients.2012

    • Author(s)
      Adachi T
    • Journal Title

      Nephrology

      Volume: 17 Issue: 8 Pages: 689-694

    • DOI

      10.1111/j.1440-1797.2012.01642.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Proteinuria elevates asymmetric dimethylarginine levels via protein arginine methyltransferase-1 overexpression in a rat model of nephrotic syndrome.2012

    • Author(s)
      Kaida Y, Okuda S, et al.
    • Journal Title

      Life Sci.

      Volume: 91 Issue: 9-10 Pages: 301-305

    • DOI

      10.1016/j.lfs.2012.06.015

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of advanced glycation end products (AGEs) and oxidative stress in vascular complications in diabetes2012

    • Author(s)
      Yamagishi SI, Maeda S, Matsui T, Ueda S, Fukami K, Okuda S
    • Journal Title

      Biochim Biophys Acta

      Volume: 1820 Issue: 5 Pages: 663-671

    • DOI

      10.1016/j.bbagen.2011.03.014

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new vasculitis activity score for predicting deathin myeloperoxidase-antineutrophil cytoplasmic antibody associated vasculitis patients.2011

    • Author(s)
      Koike K, Fukami K, Yonemoto K, Iwatani R, Obara N, Ueda K,Toyonaga M, Ueda S, Ohara A, Takeda K, Yamagishi S, Okuda S.
    • Journal Title

      Am J Nephrol.

      Volume: 35(1) Pages: 1-6

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Beneficial cardiometabolic actions of telmisartan plus amlodipine therapy in elderly patients with poorly controlled hypertension.2011

    • Author(s)
      Bekki H, Yamamoto K, Sone M, Homma T, Nakata M, Nohara M, Fukami K, Okuda S, Yamagishi S. C
    • Journal Title

      lin Cardiol.

      Volume: 34(4) Pages: 261-5

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Tissue level of advanced glycation end products (AGEs) is an independent determinant of high sensitive C-reactive protein levels in hemodialysis patients.2011

    • Author(s)
      Makio Nagano, Kei Fukami, Sho-ichi Yamagishi, Kazuko Sakai, Yusuke Kaida, Takafumi Matsumoto, Takuma Hazama, Masahiro Tanaka,1 Seiji Ueda, and Seiya Okuda.
    • Journal Title

      Nephrology.

      Volume: 16(3) Pages: 299-303

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pigment epithelium-derived factor (PEDF) inhibits proximal tubular cell injury in early diabetic nephropathy by suppressing advanced glycation end products (AGEs)-receptor (RAGE) axis.2011

    • Author(s)
      Maeda S, Matsui T, Takeuchi M, Yoshida Y, Yamakawa R, Fukami K, Yamagishi SI.
    • Journal Title

      Pharmacol Res.

      Volume: 63(3) Pages: 241-8

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] A new vasculitis activity score for predicting death in myeloperoxidase-antineutrophil cytoplasmic antibody associated vasculitis patients2011

    • Author(s)
      Koike K, Fukami K, Yonemoto K, Iwatani R, Obara N, Ueda K, Toyonaga M, Ueda S, Ohara A, Takeda K, Yamagishi S, Okuda S
    • Journal Title

      Am J Nephrol

      Volume: 35 Issue: 1 Pages: 1-6

    • DOI

      10.1159/000334357

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Beneficial cardiometabolic actions of telmisartan plus amlodipine therapy in elderly patients with poorly controlled hypertension2011

    • Author(s)
      Bekki H, Yamamoto K, Sone M, Homma T, Nakata M, Nohara M, Fukami K, Okuda S, Yamagishi S
    • Journal Title

      Clin Cardiol

      Volume: 34 Issue: 4 Pages: 261-265

    • DOI

      10.1002/clc.20855

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tissue level of advanced glycation end products (AGEs) is an independent determinant of high sensitive C-reactive protein levels in hemodialysis patients.2011

    • Author(s)
      Nagano M, Fukami K
    • Journal Title

      Nephrology

      Volume: 16 Pages: 299-303

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of enzyme-linked immunosorbent assay system for PEDF and its clinical utility2010

    • Author(s)
      Kei Fukami, Sho-ichi Yamagishi
    • Journal Title

      Curr Mol Med

      Volume: 10 Pages: 317-320

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interstitial Foxp3-positive T cells may predict renal survival in patients with myeroperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomemlonephritis2010

    • Author(s)
      Junko Yoshimura, Kei Fukami
    • Journal Title

      Clin Exp Phannacol Physiol

      Volume: 37 Pages: 879-883

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] DNA aptamer raised against AGEs improves diabetic nephropathy in KK/Ay-Ta miceKei Fukami2013

    • Author(s)
      Sho-ichi Yamagishi, Yusuke Kaida, Yuichiro Higashimoto, Masayoshi Takeuchi, Hiroyoshi Inoue, Seiya Okuda.
    • Organizer
      日本循環器学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] DNA aptamer raised against AGEs improves diabetic nephropathy in KK/Ay-Ta mice2013

    • Author(s)
      深水 圭
    • Organizer
      日本循環器学会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] DNA aptamer raised against AGEs improves diabetic nephropathy in KK/Ay-Ta miceNana Obara2012

    • Author(s)
      Kei Fukami, Sho-ichi Yamagishi, Yusuke Kaida, Yuichiro Higashimoto, Masayoshi Takeuchi, Seiji Ueda, Hiroyoshi Inoue, Seiya Okuda.
    • Organizer
      2012 International Symposium on the Maillard Reaction | IMARS.
    • Place of Presentation
      Nancy, France
    • Related Report
      2012 Final Research Report
  • [Presentation] DNA aptamer raised against AGEs improves diabetic nephropathy in KK/Ay-Ta mice2012

    • Author(s)
      Obara N
    • Organizer
      International Maillard Reaction Society
    • Place of Presentation
      France
    • Related Report
      2012 Annual Research Report
  • [Presentation] DNA aptamers raised against AGEs improve diabetic nephropathy in KK/Ay-Ta mice2011

    • Author(s)
      Yusuke Kaida, Kei Fukami
    • Organizer
      アメリカ腎臓病学会
    • Place of Presentation
      アメリカ・フィラデルフィア
    • Year and Date
      2011-11-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] AGEs-DNAアプタマーは糖尿病腎症の糸球体硬化を改善する2011

    • Author(s)
      甲斐田裕介、深水圭
    • Organizer
      日本腎臓学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-05-12
    • Related Report
      2011 Annual Research Report
  • [Presentation] DNA aptamers raised against AGEs improve diabetic nephropathy in KK/Ay-Ta mice2011

    • Author(s)
      Kei Fukami, Sho-ichi Yamagishi
    • Organizer
      国際腎臓病学会
    • Place of Presentation
      カナダ・バンクーバー
    • Year and Date
      2011-04-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] DNA aptamers raised against AGEs improve diabetic nephropathy in KK/Ay-Ta mice.2011

    • Author(s)
      Yusuke Kaida , Kei Fukami, Sho-ichiYamagishi, Yuichiro Higashimoto, Nana Obara, Ryotaro Ando, Yosuke Nakayama, Masayoshi Takeuchi, Takanori Matsui, Seiji Ueda, Hiroyoshi Inoue, Seiya Okuda.
    • Organizer
      American Society of Nephrology.
    • Place of Presentation
      Philadelphia, Pennsylvania
    • Related Report
      2012 Final Research Report
  • [Presentation] AGEs-DNAアプタマーは糖尿病腎症の糸球体硬化を改善する2011

    • Author(s)
      甲斐田裕介、深水圭、上田誠二、山岸昌一、奥田誠也
    • Organizer
      日本腎臓学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] DNA aptamers raised against AGEs improve diabetic nephropathy in KK/Ay-Ta miceDNA aptamers raised against AGEs improve diabetic nephropathy in KK/Ay-Ta miceKei Fukami, Sho-ichi Yamagishi, Yuichiro Higashimoto2011

    • Author(s)
      Yusuke Kaida, Ryuji Iwatani, Ryotaro Ando, Yosuke Nakayama, Masayoshi Takeuchi, Takanori Matsui, Seiji Ueda, Hiroyoshi Inoue, Seiya Okuda.
    • Organizer
      International Society of Nephrology.
    • Place of Presentation
      Vancouver, Canada.
    • Related Report
      2012 Final Research Report
  • [Book] アログリプチンからリナグリプチンへの切り替え例での臨床的有用性についてー血液透析患者における検討―2013

    • Author(s)
      深水 圭
    • Total Pages
      5
    • Publisher
      Ther. Res.
    • Related Report
      2012 Annual Research Report
  • [Book] Visual糖尿病臨床のすべて 糖尿病性腎症のすべて;腎症の治療・管理・対策とそのエビデンス深水2012

    • Author(s)
      圭、奥田誠也
    • Publisher
      中山書店
    • Related Report
      2012 Final Research Report
  • [Book] AGEs と老化 Chapter 1 AGEs 化反応の基礎AGEs 受容体 深水 圭2012

    • Author(s)
      奥田誠也
    • Publisher
      メディカルレビュー社
    • Related Report
      2012 Final Research Report
  • [Book] 腎と透析 糖尿病性腎症への挑戦AGE の腎症進展における役割と治療法開発 への期待 深水 圭2012

    • Author(s)
      奥田誠也
    • Related Report
      2012 Final Research Report
  • [Book] Nutritional and Therapeutic Interventions for Diabetes and Metabolic Syndrome Chapter 12 P An Overview of Diabetic NephropathyKei Fukami2012

    • Author(s)
      Sho-ichi Yamagishi
    • Related Report
      2012 Final Research Report
  • [Book] 糖尿病性腎症のすべて;腎症の治療・管理・対策とそのエビデンス2012

    • Author(s)
      深水 圭
    • Total Pages
      8
    • Publisher
      Visual糖尿病臨床のすべて 中山書店
    • Related Report
      2012 Annual Research Report
  • [Book] Chapter 1 AGEs化反応の基礎、AGEs受容体2012

    • Author(s)
      深水 圭
    • Total Pages
      9
    • Publisher
      メディカルレビュー
    • Related Report
      2012 Annual Research Report
  • [Book] AGEの腎症進展における役割と治療法開発への期待2012

    • Author(s)
      深水 圭
    • Total Pages
      5
    • Publisher
      腎と透析
    • Related Report
      2012 Annual Research Report
  • [Book] An Overview of Diabetic Nephropathy2012

    • Author(s)
      深水 圭
    • Total Pages
      9
    • Publisher
      Nutritional and Therapeutic Interventions for Diabetes and Metabolic Syndrome
    • Related Report
      2012 Annual Research Report
  • [Book] An Overview of Diabetic Nephropathy Nutritional and Therapeutic Interventions for Diabetes and Metabolic Syndrome2012

    • Author(s)
      Kei Fukami, Sho-ichi Yamagishi
    • Total Pages
      9
    • Publisher
      ACADEMIC PRESS
    • Related Report
      2011 Annual Research Report
  • [Book] 日本臨床腎臓症候群(下巻) 糖尿病にみられる急性腎不全2011

    • Author(s)
      奥田誠也
    • Publisher
      深水圭
    • Related Report
      2012 Final Research Report
  • [Book] 糖尿病と酸化ストレス(メディカルレビュー)P 糖尿病患者の酸化ストレスマーカー・AGE/PEDF2011

    • Author(s)
      山岸昌一、奥田誠也
    • Publisher
      深水圭
    • Related Report
      2012 Final Research Report
  • [Book] テルミサルタンのすぐれた降圧効果と高い忍容性2011

    • Author(s)
      山岸昌一、戸次久敏、山本喜一郎、曽根正好、中田真詩、野原正敏、深水圭、奥田誠也血圧第18巻、第7号
    • Related Report
      2012 Final Research Report
  • [Book] 留米医学会雑誌 終末糖化産物からみた慢性腎臓病(CKD)の病態解明と治療戦略2011

    • Author(s)
      深水圭久
    • Related Report
      2012 Final Research Report
  • [Book] 日本臨床腎臓症候群(下巻)糖尿病にみられる急性腎不全2011

    • Author(s)
      深水圭、奥田誠也
    • Total Pages
      4
    • Publisher
      日本臨床社
    • Related Report
      2011 Annual Research Report
  • [Book] 糖尿病患者の酸化ストレスマーカー・AGE/PEDF糖尿病と酸化ストレス2011

    • Author(s)
      深水圭、山岸昌一、奥田誠也
    • Total Pages
      5
    • Publisher
      メディカルレビュー
    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] AGE特異的アプタマーの腎疾患治療用途2013

    • Inventor(s)
      深水 圭
    • Industrial Property Rights Holder
      深水 圭
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-03-21
    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] AGE特異的アプタマーの腎疾患治療用途2011

    • Inventor(s)
      深水圭
    • Industrial Property Rights Holder
      深水圭、山岸昌一、井上浩義、奥田誠也
    • Filing Date
      2011-11-24
    • Related Report
      2012 Final Research Report
    • Overseas

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Published: 2010-08-23   Modified: 2019-07-29  

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