The role of lysosomal proteases in podocytes

2014 Fiscal Year Final Research Report

• Project/Area Number: 24790856
• 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, 非常勤助教 (80599895)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: ポドサイト / オートファジー / カテプシンL / カテプシンD

Outline of Final Research Achievements

Injury and loss of podocytes are major risk factors for renal failure. In this study, we aim to investigate the role of lysosomal proteases, cathepsin L (CL) and D (CD) in podocytes. Previous studies showed that up-regulated CL in podocytes is required for the development of proteinuria in mice. We examined the doxorubicin induced nephrosis and glomerulosclerosis model on CL knockout mice.　Our findings suggested that CL-mediated proteolysis plays a role in the development of glomerulosclerosis. The role of CD in podocytes has not been previously explored. We generated podocyte-specific CD knockout mice. These mice developed proteinuria and glomerulosclerosis because of the presence of lysosomal storage disease that progressively worsens with aging. We also discovered that CD deficiency in podocytes leads to apoptotic cell death.
This strongly indicates that CL and CD enzymatic activity in podocytes is generally essential for protein turnover and autophagy homeostasis.

Free Research Field

腎臓内科学