Exogenous Administration of Low-Dose Lipopolysaccharide Potentiates Liver Fibrosis in a Choline-Deficient l-Amino-Acid-Defined Diet-Induced Murine Steatohepatitis Model.

• 資料種別: 博士論文
• タイトル: Exogenous Administration of Low-Dose Lipopolysaccharide Potentiates Liver Fibrosis in a Choline-Deficient l-Amino-Acid-Defined Diet-Induced Murine Steatohepatitis Model.
• 著者・編者: Nakanishi, Keisuke; Kaji, Kosuke; Kitade, Mitsuteru; Kubo, Takuya; Furukawa, Masanori; Saikawa, Soichiro; Shimozato, Naotaka; Sato, Shinya; Seki, Kenichiro; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Yoshiji, Hitoshi
• 著者標目: Nakanishi, Keisuke; Kaji, Kosuke; Kitade, Mitsuteru; Kubo, Takuya; Furukawa, Masanori; Saikawa, Soichiro; Shimozato, Naotaka; Sato, Shinya; Seki, Kenichiro; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Yoshiji, Hitoshi
• 出版事項: MDPI
• 出版年月日等: 2019-06-03
• 出版年（W3CDTF）: 2019-06-03
• 並列タイトル等: リポポリサッカライドの外因性投与はコリン欠乏 L-アミノ酸置換食誘発脂肪性肝炎モデルマウスにおいて肝線維化を促進する
• タイトル（掲載誌）: International journal of molecular sciences
• 巻号年月日等（掲載誌）: 20 11
• 掲載巻: 20
• 掲載号: 11
• 掲載ページ: Article No.2724-
• ISSN（掲載誌）: ISSN : 1422-0067
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2020-03-16
• 報告番号: 甲第738号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: nonalcoholic steatohepatitis; lipopolysaccharide; choline-deficient l-amino-acid-defined diet; toll-like receptor; NF-κB; fibrosis
• 対象利用者: 一般
• 一般注記: type:Thesis; Various rodent models have been proposed for basic research; however, the pathogenesis of human nonalcoholic steatohepatitis (NASH) is difficult to closely mimic. Lipopolysaccharide (LPS) has been reported to play a pivotal role in fibrosis development during NASH progression via activation of toll-like receptor 4 (TLR4) signaling. This study aimed to clarify the impact of low-dose LPS challenge on NASH pathological progression and to establish a novel murine NASH model. C57BL/6J mice were fed a choline-deficient l-amino-acid-defined (CDAA) diet to induce NASH, and low-dose LPS (0.5 mg/kg) was intraperitoneally injected thrice a week. CDAA-fed mice showed hepatic CD14 overexpression, and low-dose LPS challenge enhanced TLR4/NF-κB signaling activation in the liver of CDAA-fed mice. LPS challenge potentiated CDAA-diet-mediated insulin resistance, hepatic steatosis with upregulated lipogenic genes, and F4/80-positive macrophage infiltration with increased proinflammatory cytokines. It is noteworthy that LPS administration extensively boosted pericellular fibrosis with the activation of hepatic stellate cells in CDAA-fed mice. Exogenous LPS administration exacerbated pericellular fibrosis in CDAA-mediated steatohepatitis in mice. These findings suggest a key role for LPS/TLR4 signaling in NASH progression, and the authors therefore propose this as a suitable model to mimic human NASH.; 博士（医学）・甲第738号・令和2年3月16日; © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).; identifier:International journal of molecular sciences Vol.20 No.11 Article No.2724 (2019 Jun); identifier:14220067; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3732; identifier:International journal of molecular sciences, 20(11): Article No.2724
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.3390/ijms20112724
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

目次

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3732/1/01%e7%94%b2738%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3732/2/02%e7%94%b2738%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3732/3/03%e7%94%b2738%e6%9c%ac%e6%96%87.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3732/4/04%e7%94%b2738Supplementary%20Table1.pdf fulltext