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Development of a new therapy for lifestyle-related CKD targeting autophagy recycling system

Research Project

Project/Area Number 17H04188
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

ISAKA YOSHITAKA  大阪大学, 医学系研究科, 教授 (00379166)

Co-Investigator(Kenkyū-buntansha) 木村 友則  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 難治性疾患研究開発・支援センター, センター長 (00631300)
高橋 篤史  大阪大学, 医学部附属病院, 助教 (10704786)
高畠 義嗣  大阪大学, 医学系研究科, 講師 (30403075)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Keywordsオートファジー / インフラマソーム / 尿細管 / 慢性腎臓病 / 尿細管障害 / 生活習慣病 / 糖尿病 / 脂質異常 / リソソーム
Outline of Final Research Achievements

It has been thought that autophagy is induced by starvation, etc. and nonspecifically digests proteins and the like. However, even in the case of overnutrition such as obesity, lipid abnormalities and hyperuricemia, denatured proteins and abnormal mitochondria to be digested. , Etc. are increased in renal tubular cells, so that the steady-state autophagy activity is increased. However, it was found that if such a state persists, the autophagy-lysosomal system becomes stagnant, the autophagy activation is impaired during stress, the renal protective effect of autophagy does not work, and renal damage progresses.

Academic Significance and Societal Importance of the Research Achievements

定常レベルのオートファジーは尿細管細胞の恒常性の維持を担うとともに、ストレス時には、傷害をうけた細胞内小器官や変性蛋白をオートファジー・リソソーム系により消化することにより、腎障害を抑制する。加齢や肥満・脂質異常など生活習慣病に伴う腎障害の共通メカニズムとして、定常レベルのオートファジー活性が常に上昇しているために、オートファジー予備能が低下し、ストレス下でのオートファジー活性化が不十分となり、尿細管細胞に対する保護作用が働かず、炎症が惹起されるということを見出した。オートファジー予備能にも注目した治療法の開発につながると考えられた。

Report

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

    (4 results)

All 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] Antioxidant role of autophagy in maintaining the integrity of glomerular capillaries.2018

    • Author(s)
      Matsuda J, Namba T, Takabatake Y, Kimura T, Takahashi A, Yamamoto T, Minami S, Sakai S, Fujimura R, Kaimori JY, Matsui I, Hamano T, Fukushima Y, Matsui K, Soga T, Isaka Y.
    • Journal Title

      Autophagy

      Volume: 14 Issue: 1 Pages: 53-65

    • DOI

      10.1080/15548627.2017.1391428

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipophagy maintains energy homeostasis in the kidney proximal tubule during prolonged starvation2017

    • Author(s)
      Minami Satoshi、Yamamoto Takeshi、Takabatake Yoshitsugu、Takahashi Atsushi、Namba Tomoko、Matsuda Jun、Kimura Tomonori、Kaimori Jun-ya、Matsui Isao、Hamano Takayuki、Takeda Hiroaki、Takahashi Masatomo、Izumi Yoshihiro、Bamba Takeshi、Matsusaka Taiji、Niimura Fumio、Isaka Yoshitaka
    • Journal Title

      Autophagy

      Volume: 13 Issue: 10 Pages: 1629-1647

    • DOI

      10.1080/15548627.2017.1341464

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autophagy Inhibits the Accumulation of Advanced Glycation End Products by Promoting Lysosomal Biogenesis and Function in the Kidney Proximal Tubules2017

    • Author(s)
      Takahashi Atsushi、Takabatake Yoshitsugu、Kimura Tomonori、Maejima Ikuko、Namba Tomoko、Yamamoto Takeshi、Matsuda Jun、Minami Satoshi、Kaimori Jun-ya、Matsui Isao、Matsusaka Taiji、Niimura Fumio、Yoshimori Tamotsu、Isaka Yoshitaka
    • Journal Title

      Diabetes

      Volume: 66 Issue: 5 Pages: 1359-1372

    • DOI

      10.2337/db16-0397

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] オートファジーからみた慢性腎臓病治療の新しい知見2018

    • Author(s)
      猪阪善隆
    • Organizer
      7.第61回日本腎臓学会学術総会
    • Related Report
      2018 Annual Research Report
    • Invited

URL: 

Published: 2017-04-28   Modified: 2021-12-27  

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