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A new therapeutic target for diabetic kidney disease via Sirt3 activation by CD38 inhibiton.

Research Project

Project/Area Number 17K16104
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionKanazawa Medical University

Principal Investigator

OGURA Yoshio  金沢医科大学, 医学部, 助教 (30760409)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords糖尿病腎症 / 酸化ストレス / ミトコンドリア / Sirt3 / CD38 / 腎臓学
Outline of Final Research Achievements

We focused on Sirt3, mainly located in mitochondria and plays an important role in anti-oxidative stress and cellular metabolism, and NAD+-degrading enzyme CD38 as novel therapeutic targets for diabetic kidney disease, and aimed to elucidate whether the inhibition of CD38 could ameliorate renal injury through the increase of NAD+ and the activation of Sirt3. We have shown that administration of a CD38 inhibitor (flavonoid "apigenin") to renal tubular cells in diabetic rats under high glucose culture can inhibit the progression of diabetic kidney disease, and the results have been published in Redox reports 2018, received the Japanese Society of Anti-Aging Research Encouragement Award 2019, presented at the American Diabetes Association meeting and other international conferences, and submitted to Aging 2020, which was accepted in May and will be published later.

Academic Significance and Societal Importance of the Research Achievements

我が国では糖尿病患者数の増加とともに糖尿病腎症(以下腎症)を有する患者数が増加している。腎症を原因として新規透析療法を導入される患者数は第1位であり,腎症の克服は解決していくべき課題であると考えられる。現在,腎症に対する治療は、血糖・血圧・脂質管理を中心とする包括的治療が推奨されているが,未だ十分であるとはいい難く,新規治療の開発が望まれていた.
今回我々はCD38とSirt3という今までにない腎症の新たな治療標的に着目し,CD38抑制効果を持つフラボノイドの経口投与によって腎症の進展を抑制できる可能性を見出した.近い将来に,簡便に,我々の腎症改善の効果を期待できうる成果を得たと考えている.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 3 results) Remarks (1 results)

  • [Journal Article] Renal mitochondrial oxidative stress is enhanced by the reduction of Sirt3 activity, in Zucker diabetic fatty rats2018

    • Author(s)
      Ogura Yoshio、Kitada Munehiro、Monno Itaru、Kanasaki Keizo、Watanabe Ai、Koya Daisuke
    • Journal Title

      Redox Report

      Volume: 23 Issue: 1 Pages: 153-159

    • DOI

      10.1080/13510002.2018.1487174

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] CD38 inhibittion decrease renal oxidative stress in diabetic kidney disease by restoreing of Sirt3 activation.2019

    • Author(s)
      Yoshio Ogura, Munehiro Kitada, Itaru Monno, Daisuke Koya
    • Organizer
      International Society of Nephrology (ISN) World Congress of Nephrology2019.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 糖尿病性腎臓病に対する新規治療標的としてのNAD分解酵素CD38の抑制とSirt3の活性化の意義の解明~尿細管細胞ミトコンドリア酸化ストレスの軽減とアンチエイジングの観点から~2019

    • Author(s)
      小倉慶雄
    • Organizer
      第19回日本抗加齢医学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] NAD分解酵素CD38制御が糖尿病腎症進展抑制の新規治療標的となりうるかの検証2019

    • Author(s)
      小倉慶雄,北田宗弘,門野 至,古家 大祐
    • Organizer
      第31回日本糖尿病性腎症研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] CD38抑制によるSirt3の活性化を介した糖尿病腎尿細管細胞保護効果の検証2019

    • Author(s)
      小倉慶雄,北田宗弘,門野 至,古家 大祐
    • Organizer
      第34回日本糖尿病合併症学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] NAD分解酵素CD38の抑制はSirt3を介して糖尿病腎臓病において腎酸化ストレスを軽減する2019

    • Author(s)
      小倉慶雄 北田宗弘 門野 至 古家 大祐
    • Organizer
      第23回日本心血管内分泌代謝学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アピゲニンによるCD38抑制はSirt3の活性化を誘導して糖尿病腎尿細管細胞保護効果を発揮する2018

    • Author(s)
      小倉慶雄、北田宗弘、門野至、渡邊愛、古家大祐
    • Organizer
      第61回日本糖尿病学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Renal mitochondrial oxidative stress induced by NAD+-dependent Sirtuins inactivation via overexpression of CD38 (NADase) activation inDKD.2018

    • Author(s)
      Yoshio Ogura, Munehiro Kitada, Itaru Monno, Ai Watanabe, Daisuke Koya
    • Organizer
      第78回米国糖尿病学会議
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Overexpression of CD38 (NADase) in diabetic kidney disease results in renal mitochondrial oxidative stress and pathologies via NAD+-dependent Sirt3 inactivation2018

    • Author(s)
      Yoshio Ogura, Munehiro Kitada, Itaru Monno, Daisuke Koya
    • Organizer
      第54回欧州糖尿病学会議
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Sirt3機能低下は糖尿病腎近位尿細管におけるミトコンドリア酸化ストレスの増強に寄与する2017

    • Author(s)
      小倉慶雄、北田宗弘、鈴木妙子、門野至、渡邊愛、古家大祐
    • Organizer
      第60回日本糖尿病学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 糖尿病腎近位尿細管におけるミトコンドリア酸化ストレスの増強はSirt3機能の低下が関与する。2017

    • Author(s)
      小倉慶雄、北田宗弘、鈴木妙子、古家大祐
    • Organizer
      第17回日本抗加齢医学会総会
    • Related Report
      2017 Research-status Report
  • [Remarks] 糖尿病・内分泌内科学 小倉慶雄助教が第19回日本抗加齢医学会総会において

    • URL

      https://www.kanazawa-med.ac.jp/blog/2019/06/-192019.html?fi=1

    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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