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Direct intervention of incretin to protect the blood-retinal barrier - Suppression on onset and progression of diabetic retinopathy -

Research Project

Project/Area Number 25460654
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionGifu Pharmaceutical University

Principal Investigator

ADACHI TETSUO  岐阜薬科大学, 薬学部, 教授 (40137063)

Co-Investigator(Kenkyū-buntansha) HARA Hirokazu  岐阜薬科大学, 薬学部, 准教授 (30305495)
KAMIYA Tetsuro  岐阜薬科大学, 薬学部, 助教 (60453057)
Co-Investigator(Renkei-kenkyūsha) IKEDA Tsunehiko  大阪医科大学, 医学部, 教授 (70222891)
Research Collaborator YASUDA Hiroyuki  
MAKINO Junya  
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords糖尿病 / エピジェネティクス / ストレス / インクレチン / 抗酸化酵素 / 血管内皮細胞 / シグナル伝達
Outline of Final Research Achievements

Exendin-4 is an analog of the glucagon-like peptide 1 (GLP-1) and is used in the treatment of type 2 diabetes. Since human GLP-1 receptor has been identified in various cells besides pancreatic cells, exendin-4 is expected to exert extrapancreatic actions. The expression of extracellular-superoxide dismutase (EC-SOD), a major SOD isozyme that is crucially involved in redox homeostasis, is regulated by epigenetic factors. We demonstrated that exendin-4 induced the expression of EC-SOD in A549 human lung adenocarcinoma epithelial cell line and human retinal microvascular endothelial cells through demethylation of some methyl-CpG sites and histone H3 acetylation at the EC-SOD proximal promoter region, respectively. Moreover, plasma EC-SOD concentrations in diabetic patients were elevated by incretin-based therapies. Therefore, incretin-based therapies may exert direct extrapancreatic effects in order to protect blood vessels by enhancing anti-oxidative activity.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (33 results)

All 2016 2015 2014 2013 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Acknowledgement Compliant: 7 results,  Open Access: 3 results) Presentation (19 results) Remarks (2 results)

  • [Journal Article] Exendin-4 promotes extracellular-superoxide dismutase expression in A549 cells through DNA demethylation2016

    • Author(s)
      Yasuda H, Mizukami K, Hayashi M, Kamiya T, Hara H, Adachi T
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 58 Issue: 1 Pages: 34-39

    • DOI

      10.3164/jcbn.15-16

    • NAID

      130005116625

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Crosstalk mechanism among EMT, ROS, and histone acetylation in phorbol exter-treated human breast cancer MCF-7 cells2016

    • Author(s)
      Tetsuro Kamiya, Aki Goto, Eri Kurokawa, Hirokazu Hara, Tetsuo Adachi
    • Journal Title

      Oxidative Medicine and Cellular Longevity

      Volume: 2016 Issue: 1 Pages: 1284372-1284372

    • DOI

      10.1155/2016/1284372

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Caffeic acid phenethyl ester suppresses monocyte adhesion to the endothelium by inhibiting NF-κB/NOX2-derived ROS signaling2016

    • Author(s)
      Risa Nakahara, Junya Makino, Tetsuro Kamiya, Hirokazu Hara, Tetsuo Adachi
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 58 Issue: 3 Pages: 174-179

    • DOI

      10.3164/jcbn.15-94

    • NAID

      130005149372

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Suppression of EC-SOD by oxLDL during vascular smooth muscle cell proliferation2016

    • Author(s)
      Junya Makino, Rei Asai, Mao Hashimoto, Tetsuro Kamiya, Hirokazu Hara, Masayuki Ninomiya, Mamoru Koketsu, Tetsuo Adachi
    • Journal Title

      Journal of Cellular Biochemistry

      Volume: in press Issue: 11 Pages: 2496-2505

    • DOI

      10.1002/jcb.25542

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Royal jelly constituents increase the expression of extracellular-superoxide disputes through histone acetylation in monocytic THP-1 cells2016

    • Author(s)
      Junya Makino, Rie Ogasawara, Tetsuro Kamiya, Hirokazu Hara, Yukari Mitsugi, Eiji Yamaguchi, Akichika Itoh, Tetsuo Adachi
    • Journal Title

      Journal of Natural Products

      Volume: 79 Issue: 4 Pages: 1137-1143

    • DOI

      10.1021/acs.jnatprod.6b00037

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Foresight of physical development indicated by the national health and nutrition survey in Japan: An approach in terms of biomedical sciences2015

    • Author(s)
      Maehata Y, Miyamoto C, Tsukinoki T, Takahashi S, Yoshino F, Wada-Takahashi S, Yoshida A, Tanaka A, Adachi T, Igoshi N, Shiba T, Kishikawa N, Imazato T, Suzuki I, Ihara H, Shumonura H, Okabe H, Yanagisaawa T, Hosho A, Maehata E
    • Journal Title

      Int. J. Anal. Bio-Sci.

      Volume: 3 Pages: 63-72

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxidized low-density lipoprotein accelerates the destabilization of extracellular-superoxide dismutase mRNA during foam cell formation2015

    • Author(s)
      Makino J, Nii M, Kamiya T, Hara H, Adachi T
    • Journal Title

      Arch. Biochem. Biophys.

      Volume: 575 Pages: 54-60

    • DOI

      10.1016/j.abb.2015.04.001

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The involvement of endoplasmic reticulum stress in bile acid-induced hepatocellular injury2014

    • Author(s)
      Adachi T, Kaminaga T, Yasuda H, Kamiya T, Hara H
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 54 Issue: 2 Pages: 129-135

    • DOI

      10.3164/jcbn.13-46

    • NAID

      130004879352

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Plasma levels of nitric oxide metabolites are markedly reduced in normotensive men with electrocardiographically determined left ventricular hypertrophy2014

    • Author(s)
      Kamezaki F, Tsutsui M, Takahashi M, Sonoda S, Kubo T, Fujino Y, Adachi T, Abe H, Takeuchi M, Mayumi T, Otsuji Y
    • Journal Title

      Hypertension

      Volume: 64 Issue: 3 Pages: 516-522

    • DOI

      10.1161/hypertensionaha.114.03287

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] EC-SOD levels in pre-dialysis sera and the relationship with HOMA-R2014

    • Author(s)
      Maehata Y, Maehata K, Adachi T, Tanaka A, Ikoshi N, Kuroda N, Kishikawa N, Shiba T, Matsushita M, Yanagisawa T, Maehata E, Shimomura H
    • Journal Title

      Int. J. Anal. Bio-Sci.

      Volume: 2 Pages: 155-162

    • NAID

      40020305092

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of endoplasmic reticulum (ER) stress inducer thapsigargin on the expression of extracellular-superoxide dismutase in mouse 3T3-L1 adipocytes2013

    • Author(s)
      Tetsuro Kamiya, Hirokazu Hara, Tetsuo Adachi
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 52 Issue: 2 Pages: 101-105

    • DOI

      10.3164/jcbn.12-46

    • NAID

      130004466711

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epigenetic regulation of extracellular-superoxide dismutase in human monocytes.2013

    • Author(s)
      Tetsuro Kamiya, Masatomo Machiura, Junya Makino, Hirokazu Hara, Isao Hozumi, Tetsuo Adachi
    • Journal Title

      Free Radical Biology and Medicine

      Volume: in press Pages: 197-205

    • DOI

      10.1016/j.freeradbiomed.2013.04.013

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] TNFαによるDNAメチル化機構を介したEC-SOD発現調節2016

    • Author(s)
      森沢惇平,安田浩之,神谷哲朗,原宏和,足立哲夫
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      横浜
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Caffeic acid phenetyl esterのエピジェネティック作用を介するEC-SOD発現調節機構2015

    • Author(s)
      大橋敦子,安田浩之,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      第6回岐阜薬科大学機能性健康食品(蜂産品)研究講演会
    • Place of Presentation
      岐阜
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] ローヤルゼリー成分によるEC-SOD発現変動とエピジェネティクスとの関連性2015

    • Author(s)
      小笠原理恵,牧野純也,神谷哲朗,原 宏和,満木友加里,山口英士,伊藤彰近,足立哲夫
    • Organizer
      第6回岐阜薬科大学機能性健康食品(蜂産品)研究講演会
    • Place of Presentation
      岐阜
    • Year and Date
      2015-12-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト単球系細胞株THP-1細胞におけるローヤルゼリー成分によるEC-SOD発現変動とエピジェネティクスの関与2015

    • Author(s)
      牧野純也,小笠原理恵,神谷哲朗,原 宏和,満木友加里,山口英士,伊藤彰近,足立哲夫
    • Organizer
      第38回日本分子生物学会年会,第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Ten-eleven translocation 1 regulates SOD3 expression by its direct binding to human SOD3 promoter region2015

    • Author(s)
      Kamiya T, Nakahara R, Hara H, Adachi T
    • Organizer
      22nd Annual Meeting of the Society for Free Radical Biology and Medicine
    • Place of Presentation
      Bostone
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] EC-SOD expression is suppressed by treatment with oxLDL in vascular smooth muscle cells2015

    • Author(s)
      Makino J, Asai R, Kamiya T, Hara H, Adachi T
    • Organizer
      22nd Annual Meeting of the Society for Free Radical Biology and Medicine
    • Place of Presentation
      Bostone
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] TNFα suppresses EC-SOD expression through epigenetic regulation in fibroblasts2015

    • Author(s)
      Yasuda H, Morisawa S, Kamiya T, Hara H, Adachi T
    • Organizer
      22nd Annual Meeting of the Society for Free Radical Biology and Medicine
    • Place of Presentation
      Bostone
    • Year and Date
      2015-11-18
    • Related Report
      2015 Annual Research Report
  • [Presentation] Caffeic acid phenethyl esterによるエピジェネティクス制御機構を介した抗酸化酵素の発現変動2015

    • Author(s)
      大橋敦子,安田浩之,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      第127回日本薬理学会近畿支部会
    • Place of Presentation
      岐阜
    • Year and Date
      2015-06-26
    • Related Report
      2014 Research-status Report
  • [Presentation] Ten-eleven translocation 1を介したEC-SOD遺伝子のDNA脱メチル化機構2015

    • Author(s)
      神谷哲朗,仲原理沙,原 宏和,足立哲夫
    • Organizer
      第68回日本酸化ストレス学会学術集会
    • Place of Presentation
      鹿児島
    • Year and Date
      2015-06-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] 血管平滑筋細胞への酸化LDL曝露によるEC-SOD発現低下に対するluteolinの抑制効果2015

    • Author(s)
      浅井玲衣,牧野純也,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      日本生化学会中部支部例会・シンポジウム
    • Place of Presentation
      松本
    • Year and Date
      2015-05-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] エピジェネティクス制御機構を介したexendin-4によるヒト網膜血管内皮細胞EC-SODの発現調節2015

    • Author(s)
      安田浩之,林 睦菜,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      下関
    • Year and Date
      2015-05-21 – 2015-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] インクレチンのDNA脱メチル化機能によるEC-SOD発現調節2014

    • Author(s)
      安田浩之,林 睦菜,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      第26回腎とフリーラジカル研究会
    • Place of Presentation
      名古屋
    • Year and Date
      2014-09-20
    • Related Report
      2014 Research-status Report
  • [Presentation] Exendin-4のDNAメチル化制御によるEC-SOD発現調節2014

    • Author(s)
      安田浩之,水上康治,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      第60回日本薬学会東海支部大会
    • Place of Presentation
      鈴鹿
    • Year and Date
      2014-07-05
    • Related Report
      2014 Research-status Report
  • [Presentation] コーヒー含有ポリフェノールのエピジェネティクス制御能2014

    • Author(s)
      足立哲夫
    • Organizer
      全日本コーヒー協会第17回研究助成報告会
    • Place of Presentation
      東京
    • Year and Date
      2014-06-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 低酸素状態下のCOS7細胞におけるEC-SOD発現調節機構としてのエピジェネティクス2014

    • Author(s)
      服部脩平,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      日本生化学会中部支部例会・シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2014-05-24
    • Related Report
      2014 Research-status Report
  • [Presentation] ヒト単球系細胞株におけるEC-SOD遺伝子のDNAメチル化制御機構2013

    • Author(s)
      神谷哲朗,町浦雅量,牧野純也,原 宏和,足立哲夫
    • Organizer
      第66回日本酸化ストレス学会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Research-status Report
  • [Presentation] Signaling pathways related to endoplasmic reticulum stress-induced retinal endothelial permeability2013

    • Author(s)
      Adachi T, Kamamura M, Yasuda H, Teramachi M, Kamiya T, Hara H
    • Organizer
      Biennial Meeting of Society for Free Radical Research Asia 2013
    • Place of Presentation
      Tao-Yuan, Taiwan
    • Related Report
      2013 Research-status Report
  • [Presentation] エピジェネティクス制御機構を介したExendin-4によるEC-SOD発現調節

    • Author(s)
      安田浩之, 水上康治, 林 睦菜, 神谷哲朗, 原 宏和, 足立哲夫
    • Organizer
      日本酸化ストレス学会東海支部 第2回学術集会
    • Place of Presentation
      岐阜
    • Related Report
      2013 Research-status Report
  • [Presentation] ストレスに起因する網膜血管内皮細胞層透過性亢進に対するステロイド剤の抑制作用

    • Author(s)
      鎌村麻由,寺町真由美,神谷哲朗,原 宏和,足立哲夫
    • Organizer
      日本酸化ストレス学会東海支部 第2回学術集会
    • Place of Presentation
      岐阜
    • Related Report
      2013 Research-status Report
  • [Remarks] 岐阜薬科大学臨床薬剤学研究室ホームページ

    • URL

      http://www.gifu-pu.ac.jp/lab/rinyaku/index.html

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
  • [Remarks] 岐阜薬科大学臨床薬剤学研究室ホームページ

    • URL

      http://www.gifu-pu.ac.jp/lab/rinyaku/index.html

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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