| Project/Area Number |
18K15992
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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 | Asahikawa Medical College |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
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| Keywords | APE1 / 慢性腎臓病 / 抗酸化ストレス / プラスミドベクター / 腎臓病 / 腎不全 / 酸化ストレス |
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| Outline of Final Research Achievements |
Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein that controls the cellular response to oxidative stress and possesses DNA-repair functions. Its function and therapeutic prospects with respect to kidney injury are unknown. To study this, we activated APE1 during kidney injury by constructing an expression vector (pCAG-APE1), using an EGFP expression plasmid (pCAG-EGFP) as a control. We performed unilateral ureteral obstruction (UUO) as a model of tubulointerstitial fibrosis on ICR mice before each vector was administrated via retrograde renal vein injection. In this model, pCAG-APE1 injection significantly reduced histological end points including fibrosis, inflammation, tubular injury, and oxidative stress. qPCR analysis showed significantly lower expression of Casp3 and inflammation-related genes in pCAG-APE1-injected animals . Thus, therapeutic APE1 modulation might be beneficial for the treatment of renal diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は抗酸化ストレス酵素APE1の尿管結紮モデルでの腎間質線維化における役割とその作用機構を解明した。APE1は酸化ストレスの軽減のみならず、免疫機能を調整することで腎保護的に作用することを明らかにした。これらの結果より、APE1の慢性腎臓病に対する新しい治療法としての可能性が強く示唆された。
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