| Project/Area Number |
16K08931
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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 |
Laboratory medicine
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| Research Institution | University of Fukui |
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Principal Investigator |
Torii Kunio 福井大学, 学術研究院医学系部門(附属病院部), 主任臨床検査技師 (40534045)
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| Co-Investigator(Kenkyū-buntansha) |
木村 秀樹 福井大学, 学術研究院医学系部門(附属病院部), 准教授 (20283187)
岩野 正之 福井大学, 学術研究院医学系部門, 教授 (20275324)
菅谷 健 聖マリアンナ医科大学, 医学部, その他 (40381561)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | アンジオポエチン様蛋白4 / 糸球体上皮細胞 / 近位尿細管上皮 / PPAR-δ / PPAR-α / 飢餓状態 / 低酸素 / 腎疾患 / 尿細管上皮細胞 / PPAR / Angptl4 / ドキソルビシン / Ａｎｇｐｔｌ4 / 内科 / 臨床 / 腎疾患マーカー |
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| Outline of Final Research Achievements |
Angiopoietin-like protein 4 (Angptl4)is a bioactive protein secreted from muscle tissues and may reduce urinary protein amounts via its deposition into glomerular membranes. Although its expression status in kidney tissues is informative for understanding renal pathologic conditions, it has so far remained to be clarified. In this study, Angptl4 expression was upregulated in renal resident cells during starvation or hypoxia. Peroxisome proliferator-activated receptor (PPAR)-δactivation also markedly increased Angptl4 expression. In mice experiments, starvation induced Angptl4 expression, and PPAR-αappeared to be positively associated with the expression at basal or injured conditions. As for clinical examinations, serum Angptl4 levels were independently and negaitively related to serum triglyceride levels in apparently healthy subjects (n=85). Angptl4 levels in serum and urine appeared not to significantly differ in different kidney diseases including MCNS, FSGS and MN (N=78).
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| Academic Significance and Societal Importance of the Research Achievements |
慢性腎臓病患者は1000万人を超え、透析患者も33万人を超えて、その医療費は2兆円に達する状態であり、慢性腎疾患の新たな病態把握と治療開発が重要課題である。Angptl4は蛋白尿を軽減し腎疾患の治療につながる候補蛋白であるが、腎臓でのAngptl4発現動態は不明であった。本研究では、腎細胞ならびに腎組織のAngptl4発現は飢餓やPPAR-δ(脂肪酸代謝に関与する調節因子)によって著明に誘導されることが判明し、血清と尿中Angptl4は安定して測定できた。予備的解析では腎疾患群間でのAngptl4値の有意差は確認できなかったが、臨床情報を加えた詳細な解析により臨床的意義を検出できると考える。
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