Research into the relationship between autophagy lysosome degradation factors and glomerulosclerosis leading to development of new medical treatment options.

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K19466
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Juntendo University
• Principal Investigator: TAKAGI Miyuki 順天堂大学, 医学部, 特任助教 (80599895)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: ポドサイト / カテプシンD / カテプシンL / オートファジーリソソーム分解系 / 糸球体硬化

Outline of Final Research Achievements

The autophagy lysosome degradation system is essential for keeping cell homeostasis. In this study, we investigated the relationship between lysosomal proteases and glomerulosclerosis by focusing especially on cathepsins D (CD) and L (CL) in podocytes.
We analyzed podocyte specific CD knockout mice and found that CD deficiency results in dysregulation of podocyte function. Moreover, we examined the role of CL in rat podocytes using a Puromycin Aminonucleoside (PAN) nephrosis model. We discovered that CL levels and the absence of its inhibitors in podocytes affected by PAN nephrosis, are important factors contributing to podocyte damage and the development of proteinuria.Together, our results indicate that CD and CL activity are essential for quality control in podocytes.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

オートファジー・リソソーム経路による分解系関連蛋白と糸球体硬化進展メカニズムの病態の解明は、特に蛋白分解系に着目した創薬研究にも密接に関連すると考える。
また、糸球体硬化進展メカニズムの関係解明により、ポドサイト障害のバイオマーカーの検出にもつながり、さらには糸球体硬化・慢性腎臓病を減らすことが出来るような治療薬の開発への糸口となりうる。