| Project/Area Number |
16K19491
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kochi University |
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Principal Investigator |
SHIMAMURA Yoshiko 高知大学, 教育研究部医療学系臨床医学部門, 助教 (20554679)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 慢性腎臓病 / 急性腎障害 / Klotho / IL-36 / AKI / CKD / αKlotho / 加齢 / オートファジー |
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| Outline of Final Research Achievements |
The purpose of this study is to elucidate the mechanism of renal function decline with aging and the prognostic deterioration of CKD / AKI.IL-36, a newly named member of the IL-1 cytokine family, includes 3 isoforms, IL-36α,-β, and -γ, all of which bind to a heterodimer containing IL-36 receptor (IL-36R).Little is known about the role of the IL-36 axis in fibrosis during AKI to CKD progression. Our results demonstrate that IL-36α is up-regulated in renal tissues in both mouse and human AKI to CKD transition, and that IL-36α stimulates collagen type IV and CTGF in AKI to CKD transition models. Thus, IL-36α/IL-36R blockage could serve as a potential therapeutic target in AKI to CKD transition. And we reported that TXNIP, which regulates oxidative stress, was induced in tubule cells to regulate mitochondrial function in AKI. In addition, our data indicate that soluble α-Klotho level is a novel predictor for renal prognosis and of cardiac dysfunction in CKD patients.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、「加齢に伴う腎機能低下、慢性腎臓病CKD/急性腎不全AKIの予後の悪化の機序解明」を研究目的し、透析療法の回避・腎/生命予後の改善を最終的な目的としている。本研究ではIL-36が腎線維化に関与していること、またAKIにおいて新規バイオマーカーになる可能性を示唆。また酸化ストレスを調節するTXNIPがAKIにおいて尿細管細胞において発現誘導され、ミトコンドリア機能を調整していることを報告し、AKIの予後に関与する可能性が示唆された。CKD患者の臨床データの検討では、血清遊離型αKlothoが腎機能の予後予測因子、生命予後に関与する心機能障害の予測マーカーとなる可能性が示唆されている。
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