| Project/Area Number |
16K09626
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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 | Saitama Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
井上 勉 埼玉医科大学, 医学部, 准教授 (30406475)
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| Research Collaborator |
MIYAWAKI Atsushi
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 急性腎障害 / 慢性腎臓病 / 腎線維化 / アポトーシス / カスパーゼ / CCN2 / 細胞周期 / 急性腎障害(AKI) / 慢性腎臓病(CKD) / 線維化 |
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| Outline of Final Research Achievements |
The acute kidney injury (AKI) model was constructed using genetically modified mice that express and lack p35 suppressing apoptosis and CCN2 inducing fibrosis, respectively, in the tubular epithelial cells. Apoptosis suppression alleviated AKI but not chronic fibrosis in the kidney. On the other hand, suppressing apoptosis and deleting CCN2 alleviated the AKI, but fibrosis progressed more than deleting CCN2 alone. The survival of impaired tubular cells to be eliminated by apoptosis was supposed to promote fibrosis by excreting profibrotic factors. The damaged tubular cells were found to arrest in the G2 / M phase and secrete profibrotic factors. We successfully isolated this cell population using cell cycle reporter mice. We will conduct comprehensive gene expression analysis by using this cell population in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
CKDは全国で1300万人を超えると推定され、末期腎不全のハイリスク病態である。CKDから末期腎不全への経過は一律ではなく、持続的な腎機能障害の進展に加え、AKIの重積による階段状重症化により末期腎不全へ至る。よってCKD重症化の抑制には、AKIからCKDへの進展機序を明らかにする必要がある。本研究の成果から、AKIによる障害尿細管細胞がCKDへの進展を中継し、アポトーシス抑制によるAKI予防処置では障害尿細管細胞が存続し、CKDへの進展抑制が不十分であることが明らかとなった。今後の治療戦略としては、アポトーシス抑制以上のAKI予防策の開発に加え、CKD進展抑制療法を併用する必要がある。
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