| Project/Area Number |
16K09649
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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 | Osaka City University |
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Principal Investigator |
Mori Katsuhito 大阪市立大学, 大学院医学研究科, 講師 (60382040)
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| Co-Investigator(Kenkyū-buntansha) |
黒尾 誠 自治医科大学, 医学部, 教授 (10716864)
森岡 与明 大阪市立大学, 大学院医学研究科, 講師 (30382154)
庄司 哲雄 大阪市立大学, 大学院医学研究科, 准教授 (40271192)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | fetuin-A / CPP / PEW / MIA症候群 / 脂肪細胞 / 骨格筋細胞 / 栄養学 / 慢性腎臓病 / 血液透析 |
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| Outline of Final Research Achievements |
Fetuin-A is a liver-derived circulating glycoprotein that has a potent calcification-inhibitory capacity. Fetuin-A is posttranslationally modified (60 kDa fully modified fetuin-A: FM-Fet). Under calcification stress, fetuin-A can prevent calcification by forming colloidal complexes, termed CPP. Since recent reports suggest the pathological functions of CPP, we hypothesized that CPP may play reoles for malnutrition in patients with advanced CKD through dysregulation of adipocytes.
Little effects of CPP on adipocytes were observed. On the other hand, CPP dramatically increased protein expression of FM-Fet. However, CPP did not affect the mRNA expression of fetuin-A. FM-Fet contains glycosylation sites. Treatment with brefeldin-A, which blocks the transport of proteins from the endoplasmic reticulum to the Golgi complex, inhibited CPP-induced FM-Fet expression. These findings suggest that CPP could upregulate posttranslational modifications of fetuin-A.
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| Academic Significance and Societal Importance of the Research Achievements |
Fetuin-Aは石灰化抑制因子であることは良く知られているが、その過程で形成、産生されるCPPの生理的、病理学的意義は不明であった。最近、「CPP病原体説」が提唱されており、進展したCKDの栄養障害にCPPが関与している仮説を立てた。しかし脂肪細胞に対するCPPの影響は軽微であった。一方、CPPは肝fetuin-A発現に対しては顕著な効果を発揮した。この結果はCPPによるfetuin-A発現のfeedback機構の存在を示唆するものである。
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