| Project/Area Number |
18K15997
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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 | Nagoya University |
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Principal Investigator |
KARIYA TETSUYOSHI 名古屋大学, アジアサテライトキャンパス学院(医), 特任助教 (60805290)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 腹膜透析 / 腹膜機能低下 / 腹膜線維化 |
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| Outline of Final Research Achievements |
The purpose of this study is to reveal the mechanisms how TGF-beta1 induces VEGF-A, and VEGF-A causes peritoneal dysfunction in peritoneal dialysis. Sixty-six human peritoneal tissues and 136 peritoneal dialysis fluid were analyzed with microscopic examinations, immunological stains and protein measurements. Compared to the control groups, samples with peritoneal dysfunction had significantly (1) higher levels of VEGF-A and TGF-beta1 protein in peritoneal dialysis fluid, (2) increased number of CD-31-positive vascular vessels in submesothelial compact zone of peritoneal tissues, and (3) higher level of VEGF-A mRNA expression in peritoneal tissues. It was suggested that TGF-beta1-VEGF-A induction and subsequent loss of vascular integrity causes peritoneal dysfunction in peritoneal dialysis. Peritoneal fibrosis in animal model revealed that hypoxic change in macrophages of peritoneal membrane induces by TGF-β1 causes VEGF-A, resulting in increased angiogenesis and vascular permibility.
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| Academic Significance and Societal Importance of the Research Achievements |
腎臓病が進行し末期腎不全の状態になると腎臓の機能を代替する腎代替療法が必要となる。治療法の内、腹膜透析は生活の質の面で有利な治療法である。しかしながら、腹膜機能の低下は腹膜透析の継続を難しくする要因の一つである。本研究から、腹膜でのTGF-β1-VEGF-A経路の増強とそれによる血管恒常性の破綻が腹 膜機能の低下に関連しており、TGF-β1によるVEGF-Aの誘導には低酸素が関連していることが明らかとなった。今後、本研究で明らかにした経路をターゲットにした治療方法の開発が期待される。
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