2022 Fiscal Year Final Research Report
The effects of serine protease inhibition on the polycystic kidney disease
| Project/Area Number |
20K08638
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | セリンプロテアーゼ / セリンプロテアーゼ阻害薬 / 多発性嚢胞腎 / 慢性腎臓病 |
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| Outline of Final Research Achievements |
This study aimed to develop a novel therapeutic approach targeting a serine protease, a type of protein-degrading enzyme, for polycystic kidney disease (PKD), which has been the fourth leading cause of end-stage renal disease requiring dialysis. PKD model rats exhibited numerous kidney cyst formations, increased kidney weight, and impaired renal function, along with the activation of a specific serine protease (SP) in the renal tissue. Inhibitors of this SP effectively suppressed cyst enlargement and renal dysfunction. Furthermore, the SP inhibitor also inhibited the enlargement of liver cysts, for which effective treatments are currently lacking. These findings suggest that SP inhibition could potentially serve as a new therapeutic strategy for PKD, a condition that still lacks sufficient treatment options.
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| Free Research Field |
腎臓内科
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| Academic Significance and Societal Importance of the Research Achievements |
主要な透析導入の原疾患の中で、多発性嚢胞腎(PKD)は第4位（原因不明を除く）を占める。常染色体優性PKDに対してはトルバプタンにより腎嚢胞の増大と腎機能低下がある程度抑制できるが、多尿(1日4-5L)となることから、生活の質の低下が問題となる。また、時に肝機能障害を認め治療を中断せざるを得ないこともある。本研究によりPKDモデルラットの腎臓である種のセリンプロテアーゼ(SP)が活性化しており、このSPの阻害薬が嚢胞の増大と腎機能低下を抑制することが判明した。さらにSP阻害薬は現時点で治療法がない肝嚢胞の増大も抑制した。SP阻害薬がPKDに対する新たな治療戦略となる可能性が示唆された。
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