| Project/Area Number |
25461263
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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 | Kawasaki Medical School |
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Principal Investigator |
Sasaki Tamaki 川崎医科大学, 医学部, 教授 (30187124)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO SOUHACHI 川崎医科大学, 医学部, 講師 (00319948)
HARUNA YOSHISUKE 川崎医科大学, 医学部, 講師 (40341094)
SATOH MINORU 川崎医科大学, 医学部, 准教授 (70449891)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 腹膜線維化 / Wnt/β-cateninシグナル / 酸化ストレス / eNOS / Klotho / 腹膜透析 / Wnt/β-catenin経路 / klotho / CTGF / 中皮細胞EMT |
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| Outline of Final Research Achievements |
Long-term peritoneal dialysis causes peritoneal dysfunction and structural alterations, eventually leading to peritoneal fibrosis. However, the detailed mechanisms underlying the peritoneal fibrosis process have not been elucidated. Activation of the wnt/β-catenin signalling pathway has been suggested to play a pivotal role in the development of organ fibrosis. Furthermore, the endothelial nitric oxide synthase (eNOS)-NO signalling pathway may have contributed to the progression of organ fibrosis. We found out two important mechanisms underlying peritoneal fibrosis. First, under oxidative stress, the Wnt/β-catenin pathway in the peritoneum is activated with an increase of TGF-β, and mesothelial cells are transformed, accompanied by the effect on the cell cycle to promote peritoneal fibrosis. Second, disruption of the eNOS-NO signalling pathway exacerbates peritoneal fibrosis by delaying wound healing. These results may be a useful therapy for the prevention of peritoneal fibrosis.
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