| Project/Area Number |
25461229
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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 | International University of Health and Welfare |
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Principal Investigator |
Takenaka Tsuneo 国際医療福祉大学, 臨床医学研究センター, 教授 (90179656)
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| Co-Investigator(Renkei-kenkyūsha) |
Miyazaki Takshi 埼玉医科大学, 社会医学, 助教 (30265417)
Inoue Tsutomu 埼玉医科大学, 腎臓内科, 准教授 (30406475)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | クロト / ＴＲＰＣ６ / ネフリン / アンギオテンシン / 糖尿病 / 腎肥大 / 線維化 / 高血圧 / ＥＭＴ / 糸球体 / WNT / 上皮間葉転移 / PTH / ビタミンD / TGFβ |
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| Outline of Final Research Achievements |
Renoprotective actions of exogenous klotho protein supplementation were examined in adriamycin nephropethy, nephrosclerosis models.In adrimaycin nephropathy, exogenous klotho protein supplementation inhibits Wnt signaling to reduce renal angiotensin II concentration, blood pressure and proteinuria. In addition, klotho protein suppressed TGFβ signaling to decline epithelial-mesenchymal transition and renal fibrosis.
In early phase of nephrosclerosis model, klotho protein decreased renal angiotensin II concentration, blood pressure and medullary fibrosis. Klotho protein also inhibited Akt-mTOR pathway to ameliorate renal hypertrophy.
In addutuin, klotho protein interacted with parathyroid hormone (PTH) receptor to inhibit its binding to PTH itself. FGF23 increased renal klotho expression, serum and urinary klotho levels. These data suggest that FGF23 transduces its signal to reduce vitamin D activation via klotho.
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