Elucidation of mechanisms which determine selectivity of mitophagy in kidney tubular cells.
Project/Area Number |
17K16082
|
Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Kidney internal medicine
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Research Institution | Osaka University |
Principal Investigator |
Minami Satoshi 大阪大学, 医学部附属病院, 医員 (00791592)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
|
Project Status |
Completed (Fiscal Year 2019)
|
Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | オートファジー / マイトファジー / 尿細管 / 近位尿細管 / ミトコンドリア / 1型糖尿病 / 虚血再灌流 / 腎臓学 |
Outline of Final Research Achievements |
Autophagy is a self-degradation system in lysosomes. Especially, autophagic elimination of mitochondria, referred to as mitophagy, plays an important role to maintain mitochondrial quality. In this study, we established tissue-specific mitophagy monitoring mice. We also elucidated that autophagy was activated and protected mitochondrial function in kidney tubules under type 1 diabetes, hyperphosphatemia and AKI-CKD transition, whereas autophagy was repressed under type 2 diabetes. Moreover, our study suggested that mitophagy in kidney tubules was dependent at least in part on PINK1/Parkin pathway.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では組織特異的にマイトファジーをモニタリングするマウスを作成したが、このマウスを使用することで今後腎疾患に限らず様々な疾患においてマイトファジー活性を正確にモニターすることが可能である。更に遺伝学的スクリーニングや化合物ライブラリーを用いたスクリーニングと併用することによりマイトファジー制御分子機構の解明やマイトファジー活性化薬の開発の一助となることが期待される。また本研究では2型糖尿病の腎尿細管ではマイトファジーが抑制されていることが明らかとなり今後2型糖尿病性腎症に対してマイトファジーを活性化する治療法が有用であることが示唆された。
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Report
(4 results)
Research Products
(4 results)
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[Journal Article] Proximal Tubule Autophagy Differs in Type 1 and 2 Diabetes2019
Author(s)
Sakai S, Yamamoto T, Takabatake Y, Takahashi A, Namba-Hamano T, Minami S, Fujimura R, Yonishi H, Matsuda J, Hesaka A, Matsui I, Matsusaka T, Niimura F, Yanagita M, Isaka Y.
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Journal Title
J Am Soc Nephrol
Volume: 30(6)
Issue: 6
Pages: 929-945
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Autophagy Protects Kidney Proximal Tubules from Phosphate-Mediated Mitochondrial Dysfunction2018
Author(s)
Ryuta Fujimura, Takeshi Yamamoto, Yoshitsugu Takabatake, Satoshi Minami, Atsushi Takahashi, Tomoko Namba, Jun Matsuda, Shinsuke Sakai, Isao Matsui, Fumio Niimura, Taiji Matsusaka, Yoshitaka Isaka.
Organizer
American Society of Nephrology Kidney Week 2018
Related Report
Int'l Joint Research
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[Presentation] Autophagy protects kidney proximal tubules from phosphate-mediated mitochondrial dysfunction2018
Author(s)
Fujimura R, Yamamoto T, Takabatake Y, Minami S, Sakai S, Takahashi A, Namba-Hamano T, Matsuda J, Matsui I, Sakaguchi Y, Hamano T, Niimura F, Matsusaka T, Yoshimori T, Isaka Y.
Organizer
ISN Frontiers 2018
Related Report
Int'l Joint Research