| Project/Area Number |
16K09625
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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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| Research Field |
Kidney internal medicine
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| Research Institution | International University of Health and Welfare |
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Principal Investigator |
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| Research Collaborator |
Nishiyama Akira
Kobori Hiroyuki
Miyazaki Takeshi
Inoue Tsutomu
Ishii Naohito
Hayashi Matsuhiko
Suzuki Hiromichi
|
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | klotho / クロト / 多発性嚢胞腎 / 慢性腎臓病 |
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| Outline of Final Research Achievements |
Klotho binds with the AT1 receptors to suppress angiotensin signal transduction, participating in inactivating renal RAS. Exogenous klotho supplementation represses Akt-mTOR signaling to reduce renal hypertrophy and restore the autoregulatory ability of GFR in uninephrectomized sp-SHRs. Klotho supplementation inhibits HIF-1α pathway and medullary fibrosis, contributing to enhancements of pressure-natriuresis and reduction in blood pressure.
Klotho supplementation reduces blood pressure and albuminuria along with ameliorating renal RAS activation in db/db mice. Klotho inhibits IGF signalling, induces SOD expression to reduce oxidative stress, and suppresses Akt-mTOR signalling to inhibit abnormal kidney growth. Klotho inhibits TGF-β and TNF signalling, resulting in a decline in renal fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性腎臓病で腎のクロト発現やクロトの血中濃度は低下している。外因性クロト蛋白補充は、高血圧性腎硬化症のモデルや糖尿病性腎臓病のモデルで腎保護効果を発揮することを示し、臨床応用に向けた基礎データを提供した。
今後はクロト蛋白補充の適応範囲を明らかとするため、また、副作用の有無を検討するための研究を計画している。
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