Analysis of anti-fibrotic effects of lipid-responsible transcription factors and a search for new therapeutic agents -with special attention to hypoxic insults-
| Project/Area Number |
24591193
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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 | University of Fukui |
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Principal Investigator |
KIMURA Hideki 福井大学, 医学部附属病院, 准教授 (20283187)
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| Co-Investigator(Kenkyū-buntansha) |
IWANO Masayuki 福井大学, 医学部, 教授 (20275324)
KASUNO Kenji 福井大学, 医学部, 准教授 (60455243)
SUGAYA Takeshi 聖マリアンナ医科大学, 医学部, 客員教授 (40381561)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ペルオキシゾーム増殖因子活性化受容体 / 脂肪酸結合蛋白 / 近位尿細管上皮細胞 / メサンギウム細胞 / サイトカイン / アンジオテンシンⅡ受容体拮抗薬 / ドキソルビシン / 進行性腎障害 / 尿細管上皮細胞 / L-FABP / PPAR / 抗線維化作用 / 抗炎症作用 |
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| Outline of Final Research Achievements |
Proximal tubular epithelial cells (PT)and mesangial cells (MC) are closely associated with renal fibrosis. Mouse proximal tubular epithelial cells (mProx) overexpressing human liver-type fatty acid-binding protein (L-FABP) were shown to have greater tolerance to inflammatory and hypoxic insults than mProx itself. In human cultured PT and MC, telmisartan (ARB) executed PPAR-delta functions and reduced inflammatory and pro-fibrotic effects induced by some cytokines.
Cardiac fibrosis of PPAR-a KO mice was more evident than that of control mice (S129), which was enhanced by hypoxic environments, whereas renal fibrosis was scarcely observed and similar in the two mice groups. In doxorubicin-induced glomerulopathy, PPAR-a KO mice had more proteinuria and more frequent glomerulosclerosis than S129 mice.
These suggest the cell- and tissue-protective effects of lipid responsible transcription factors and its associated proteins such as PPARs and FABPs.
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] A heterozygous female with Fabry disease due to a novel alpha-galactosidase A mutation exhibits a unique synaptopodin distribution in vacuolated podocytes2015
Author(s)
N.Takahashi, S.Yokoi, K.Kasuno, A.Kogami, T.Tsukimura, T.Togawa, S.Saito, K.Ohno, M.Hara, H.Kurosawa, Y.Hirayama, T.Kurose, Y.Yokoyama, D.Mikami, H.Kimura, H.Naiki, H.Sakuraba, M.Iwano
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Peer Reviewed
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[Presentation] Beads法を用いた単離マウス糸球体における低酸素高糖刺激による糸球体mRNAの解析2014
Author(s)
高橋 直生, 糟野 健司, 上山 和子, 横井 靖二, 黒澤 寛之, 横山 由就, 三上 大輔, 木村 秀樹, 吉田 治義, 原 正則, 岩野 正之
Organizer
第５７回日本腎臓学会学術総会
Place of Presentation
横浜市 パシフィコ横浜 会議センター
Year and Date
2014-07-04 – 2014-07-06
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