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KAKEN_26430093seika.pdf
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Title |
Title |
HMGB1の可溶性受容体(sRAGE)に着目した新たな劇症肝不全治療法の開発
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Kana |
HMGB1 ノ カヨウセイ ジュヨウタイ (sRAGE) ニ チャクモクシタ アラタナ ゲキショウ カンフゼン チリョウホウ ノ カイハツ
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Romanization |
HMGB1 no kayosei juyotai (sRAGE) ni chakumokushita aratana gekisho kanfuzen chiryoho no kaihatsu
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Title |
Treatment for fulminant hepatitis focusing on soluble receptor for HMGB1 (sRAGE)
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篠田, 昌宏
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シノダ, マサヒロ
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Shinoda, Masahiro
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Affiliation |
慶應義塾大学・医学部・准教授
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Research team head
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科研費研究者番号 : 50286499
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高柳, 淳
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タカヤナギ, アツシ
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Takayanagi, Atsushi
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慶應義塾大学・医学部・共同研究員
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Research team member
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科研費研究者番号 : 80245464
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雨宮, 隆介
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アメミヤ, リュウスケ
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Romanization |
Amemiya, Ryusuke
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Affiliation |
慶應義塾大学・医学部・助教
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Research team member
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科研費研究者番号 : 60626696
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2017
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科学研究費補助金研究成果報告書
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2016
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Abstract |
核内タンパクHMGB1とその可溶性受容体(sRAGE)に着目し, 遺伝子治療などの特殊技術を駆使し本疾患の治療の研究・開発を進めた。sRAGE cDNAを組み込んだPlasmidをHEK293細胞に添加し, sRAGEの発現を確認した。sRAGEタンパクを含有する細胞上清を用いてマクロファージからのHMGB1によるTNFα分泌抑制試験を行い, コントロール群に比しsRAGE添加群において有意にTNFαを抑制する結果となり, in vitroでのsRAGEタンパクの生理活性を確認した。sRAGE Plasmid(800μg)をラット門脈内注射したところ肝逸脱酵素の低下傾向を認めた。
High-mobility group box 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. Acute liver failure is a lethal disease. We constructed plasmid encoding cDNA for sRAGE and performed in vitro and in vivo experiments to test if the plasmid works for acute liver failure. Western blot analysis showed enhanced expressions of sRAGE protein in HeLa cells transfected with plasmid. The culture supernatant of HeLa cells transfected with the plasmid inhibited TNF production from macrophages. Transfected rats showed tendency of decreased hepatic enzymes, It is possible that sRAGE is effective for the treatment for acute liver failure.
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研究種目 : 基盤研究(C)(一般)
研究期間 : 2014~2016
課題番号 : 26430093
研究分野 : 臓器移植
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