Implications of endothelial injuries and endothelial/epithelial interactions as pathogenetic mechanisms underlying progression of chronic kidney disease and its therapeutic application.
| Project/Area Number |
18H02828
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
長洲 一 川崎医科大学, 医学部, 准教授 (40412176)
城所 研吾 川崎医科大学, 医学部, 講師 (50435020)
佐藤 稔 川崎医科大学, 医学部, 准教授 (70449891)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Keywords | 慢性腎臓病 / 内皮障害 / 慢性炎症 / 酸化ストレス / Wnt/βーcatenine / NLRP3 inflammasome / Keap1/Nrf-2 / 線維化 / インフラマソーム / Keap-1/Nrf2 / Wnt / 老化 / 内皮/上皮連関 |
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| Outline of Final Research Achievements |
The main causes of chronic kidney disease (CKD), diabetes mellitus, hypertension and ageing - are commonly associated with endothelial damage. Endothelium and epithelium (podocytes and tubular epithelium) are in close proximity to each other in both glomeruli and tubules, and a functional link exists. We have explored the mechanisms by which endothelial damage disrupts the endothelial/epithelial linkage and leads to inflammation and fibrosis. We have demonstrated the beta-catenin pathway, Keap1/Nrf2 pathway and mitochondrial dysfunction are involved in this linkage. Furthermore, the possible renoprotective effect of the preservation of endothelial function was demonstrated.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性腎臓病（CKD）は末期腎不全のみならず、心血管病、認知症発症のリスク因子でもある。超高齢化社会を迎え一層の増加が危惧される。CKDの進展と合併症との連関機序を解明し、有効な予防・治療法を開発することが急がれる。CKDの病態形成に内皮障害が関わることが想定されながら、研究技術上の障壁により解明が遅れていた。私共は新規研究技術の開発に取り組んだ。その結果、生活習慣病、加齢によるCKDでは内皮障害がその発症に関与し、活性酸素種と一酸化窒素が病態形成のメディエーターとなる。内皮障害が内皮/上皮連関を破綻させ、腎障害の２大病態である「炎症」と「線維化」を惹起させ、CKDを重症化させるのかを解明した。
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Report
(4 results)
Research Products
(47 results)
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[Presentation] Nrf2 Activator, RTADh404, attenuates renal tubular Injury via Mitochondrial Protection in nephrotic model mice.2018
Author(s)
Yuji Sogawa, Hajime Nagasu, Megumi Kondo, Yoshihisa Wada, Kengo Kidokoro, Yoshisuke Haruna, Minoru Satoh, Tamaki Sasaki, Naoki Kashihara.
Organizer
55th ERA-EDTA Congress
Related Report
Int'l Joint Research
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