| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| 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.
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