Regulation of autophagy in podocyte by the transcription factor MAFB

• Project/Area Number: 18K15999
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Yamahara Kosuke 滋賀医科大学, 医学部, 特任助教 (50731915)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ポドサイト / オートファジー / MAFB / ポリアミン / 転写因子 / 糸球体上皮細胞 / 腎臓

Outline of Final Research Achievements

By regulating the transcription factor MAFB using recombinant technology, we found that MAFB has a cytoprotective effect through autophagy activation. We confirmed that MAFB induced polyamine metabolizing enzymes, increased spermidine levels, and spermidine induced autophagy. These results revealed the existence of a molecular mechanism of MAFB-spermidine-autophagy in podocytes, suggesting that it may be a new therapeutic target.

Academic Significance and Societal Importance of the Research Achievements

糸球体上皮細胞におけるオートファジーの活性化は、慢性腎臓病に対する有望な治療標的と考えられている。しかしながら、オートファジーの制御機構については不明な点が多かった。本研究により、糸球体上皮細胞で強く発現する転写因子MAFBが、ポリアミン経路の代謝を変化させることで細胞保護的なオートファジーを制御していることが明らかとなった。ポリアミンによる糸球体上皮細胞オートファジーの活性化が慢性腎臓病の新たな治療法となる可能性を示した。

Research Products

• [Int'l Joint Research] University of Freiburg/University of Hamburg-Eppendorf(ドイツ)
• [Int'l Joint Research] 武漢大学人民病院(中国)
• [Journal Article] A reciprocal regulation of spermidine and autophagy in podocytes maintains the filtration barrier (2020)
  • Author(s): Wei Liang, Kosuke Yamahara, Camila Hernando-Erhard, Simon Lagies, Nicola Wanner, Huan Liang, Christoph Schell, Bernd Kammerer, Tobias B.Huber7, Tillmann Bork
  • Journal Title: Kidney International Volume: 98 Issue: 6 Pages: 1434-1448
  • DOI: 10.1016/j.kint.2020.06.016
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 転写因子Mafbは糸球体上皮細胞のオートファジー活性を制御する (2018)
  • Author(s): 山原康佑、TillmannBork、WeiLiang、ChristophSchell、吉林護、久米真司、荒木信一、Tobias BHuber、前川聡
  • Organizer: 第61回日本腎臓学会学術総会
• [Presentation] Transcription factor MAFB is a new key regulator of podocyte autophagy (2018)
  • Author(s): Kosuke Yamahara, Tillmann Bork, Wei Liang, Christoph Schell, Shinji Kume, Mamoru Yoshibayashi, Shin-ichi Araki, Hiroshi Maegawa, Tobias B. Huber.
  • Organizer: Kidney week 2018
  • Int'l Joint Research