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Bone morphogenetic protein-binding endothelial regulator of liver sinusoidal endothelial cells induces iron overload in a fatty liver mouse model
https://asahikawa-med.repo.nii.ac.jp/records/5641
https://asahikawa-med.repo.nii.ac.jp/records/56417edf00a1-ea0a-49e9-ab52-268be8967b30
名前 / ファイル | ライセンス | アクション |
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6675.pdf (1.9 MB)
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Item type | 学術雑誌論文 / Journal Article_02(1) | |||||
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公開日 | 2017-01-16 | |||||
タイトル | ||||||
タイトル | Bone morphogenetic protein-binding endothelial regulator of liver sinusoidal endothelial cells induces iron overload in a fatty liver mouse model | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
キーワード | Hepcidin | |||||
キーワード | ||||||
主題Scheme | Other | |||||
キーワード | Iron metabolism | |||||
キーワード | ||||||
主題Scheme | Other | |||||
キーワード | Non-alcoholic fatty liver disease | |||||
キーワード | ||||||
主題Scheme | Other | |||||
キーワード | Signal regulation | |||||
キーワード | ||||||
主題Scheme | Other | |||||
キーワード | Whole-RNA sequencing | |||||
資源タイプ | ||||||
資源タイプ | journal article | |||||
著者 |
長谷部, 拓夢
× 長谷部, 拓夢× 田中, 宏樹× 澤田, 康司× 中嶋, 駿介× 大竹, 孝明× 藤谷, 幹浩× 高後, 裕 |
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著者 ローマ字 | ||||||
Hasebe, Takumu | ||||||
著者 ローマ字 | ||||||
Tanaka, Hiroki | ||||||
著者 ローマ字 | ||||||
Sawada, Koji | ||||||
著者 ローマ字 | ||||||
Nakajima, Shunsuke | ||||||
著者 ローマ字 | ||||||
Ohtake, Takaaki | ||||||
著者 ローマ字 | ||||||
Fujiya, Mikihiro | ||||||
著者 ローマ字 | ||||||
Kohgo, Yutaka | ||||||
書誌情報 |
Journal of Gastroenterology p. 1-11, 発行日 2016-06-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0944-1174 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1007/s00535-016-1237-6 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | BACKGROUND: \nNon-alcoholic fatty liver disease (NAFLD) is frequently accompanied by iron overload. However, because of the complex hepcidin-regulating molecules, the molecular mechanism underlying iron overload remains unknown. To identify the key molecule involved in NAFLD-associated iron dysregulation, we performed whole-RNA sequencing on the livers of obese mice. METHODS: \nMale C57BL/6 mice were fed a regular or high-fat diet for 16 or 48 weeks. Internal iron was evaluated by plasma iron, ferritin or hepatic iron content. Whole-RNA sequencing was performed by transcriptome analysis using semiconductor high-throughput sequencer. Mouse liver tissues or isolated hepatocytes and sinusoidal endothelial cells were used to assess the expression of iron-regulating molecules. RESULTS: \nMice fed a high-fat diet for 16 weeks showed excess iron accumulation. Longer exposure to a high-fat diet increased hepatic fibrosis and intrahepatic iron accumulation. A pathway analysis of the sequencing data showed that several inflammatory pathways, including bone morphogenetic protein (BMP)-SMAD signaling, were significantly affected. Sequencing analysis showed 2314 altered genes, including decreased mRNA expression of the hepcidin-coding gene Hamp. Hepcidin protein expression and SMAD phosphorylation, which induces Hamp, were found to be reduced. The expression of BMP-binding endothelial regulator (BMPER), which inhibits BMP-SMAD signaling by binding BMP extracellularly, was up-regulated in fatty livers. In addition, immunohistochemical and cell isolation analyses showed that BMPER was primarily expressed in the liver sinusoidal endothelial cells (LSECs) rather than hepatocytes. CONCLUSIONS: \nBMPER secretion by LSECs inhibits BMP-SMAD signaling in hepatocytes and further reduces hepcidin protein expression. These intrahepatic molecular interactions suggest a novel molecular basis of iron overload in NAFLD. |
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注記 | ||||||
内容記述タイプ | Other | |||||
注記 | This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) \n2016 Jun 30.Epub |
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資源タイプ | ||||||
内容記述タイプ | Other | |||||
資源タイプ | text | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
フォーマット | ||||||
内容記述タイプ | Other | |||||
内容記述 | application/pdf | |||||
ID(XooNIps) | ||||||
27364348 | ||||||
閲覧数(XooNIps) | ||||||
686 | ||||||
ダウンロード数(XooNIps) | ||||||
956 |