| Project/Area Number |
18K15998
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 慢性腎臓病 / ポドサイト / リソソーム / CKD / 糸球体上皮細胞 |
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| Outline of Final Research Achievements |
The number of patients with chronic kidney disease (CKD) in Japan is increasing, and elucidating the pathogenesis of CKD is an important research issue. Proteinuria, which is a diagnostic criterion for CKD, is mainly caused by podocyte injury, and maintaining intracellular homeostasis is important for podocytes, which do not have the ability to divide and regenerate. In this study, we hypothesized that the enhancement of lysosome function, which is responsible for intracellular proteolysis, would act cytoprotectively against podocyte injury in CKD. We found that activation of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, suppressed podocyte damage. This suggests that inhibition of podocyte damage through TFEB-mediated activation of lysosomal biogenesis may be a new therapeutic strategy for CKD.
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| Academic Significance and Societal Importance of the Research Achievements |
わが国の慢性腎臓病（CKD）患者数は増加の一途を辿っている。CKDとは糸球体濾過量の低下、蛋白尿の持続により定義される疾患群で、その病態は多種多様である。しかし、蛋白尿の主な原因となるのは糸球体スリット膜を形成するポドサイトの障害であり、この障害を抑制する機構を解明すれば、すなわち多くのCKD患者にとっての新たな治療法の開発につながると考えられる。今回、分裂能を有さないポドサイトにおいて、細胞内の蛋白分解を担うリソソームの転写因子TFEB活性化による細胞保護効果が明らかとなった。TFEBによるリソソームの活性化を介したポドサイト障害の抑制がCKDの新たな治療戦略になり得る可能性が示唆された。
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