Lenvatinib prevents liver fibrosis by inhibiting hepatic stellate cell activation and sinusoidal capillarization in experimental liver fibrosis.

• 資料種別: 博士論文
• タイトル: Lenvatinib prevents liver fibrosis by inhibiting hepatic stellate cell activation and sinusoidal capillarization in experimental liver fibrosis.
• 著者・編者: Ogawa, Hiroyuki; Kaji, Kosuke; Nishimura, Norihisa; Takagi, Hirotetsu; Ishida, Koji; Takaya, Hiroaki; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• 著者標目: Ogawa, Hiroyuki; Kaji, Kosuke; Nishimura, Norihisa; Takagi, Hirotetsu; Ishida, Koji; Takaya, Hiroaki; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Yoshiji, Hitoshi
• 出版事項: John Wiley & Sons
• 出版年月日等: 2021-04
• 出版年（W3CDTF）: 2021-04
• 並列タイトル等: レンバチニブは実験的肝線維症において肝星細胞の活性化と類洞毛細血管化を阻害することにより肝線維化を抑制する。
• タイトル（掲載誌）: Journal of cellular and molecular medicine Vol. No. p.- (2021 Apr)
• 巻号年月日等（掲載誌）: 25 8
• 掲載巻: 25
• 掲載号: 8
• 掲載ページ: 4001-4013
• ISSN（掲載誌）: ISSN : 1582-1838
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2022-03-15
• 報告番号: 甲第812号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: angiogenesis; hepatic stellate cell; lenvatinib; liver fibrosis; PDGF; VEGF
• 対象利用者: 一般
• 一般注記: type:Thesis; Molecular targeted agents are pharmacologically used to treat liver fibrosis and have gained increased attention. The present study examined the preventive effect of lenvatinib on experimental liver fibrosis and sinusoidal capillarization as well as the in vitro phenotypes of hepatic stellate cells. LX-2, a human stellate cell line, was used for in vitro studies. In vivo liver fibrosis was induced in F344 rats using carbon tetrachloride by intraperitoneal injection for 8 weeks, and oral administration of lenvatinib was started two weeks after initial injection of carbon tetrachloride. Lenvatinib restrained proliferation and promoted apoptosis of LX-2 with suppressed phosphorylation of extracellular signal-regulated kinase 1/2 and AKT. It also down-regulated COL1A1, ACTA2 and TGFB1 expressions by inhibiting the transforming growth factor-β1/Smad2/3 pathway. Treatment with lenvatinib also suppressed platelet-derived growth factor-BB-stimulated proliferation, chemotaxis and vascular endothelial growth factor-A production, as well as basic fibroblast growth factor-induced LX-2 proliferation. In vivo study showed that lenvatinib attenuated liver fibrosis development with reduction in activated hepatic stellate cells and mRNA expression of profibrogenic markers. Intrahepatic neovascularization was ameliorated with reduced hepatic expressions of Vegf1, Vegf2 and Vegfa in lenvatinib-treated rats. Collectively, these results suggest the potential use of lenvatinib as a novel therapeutic strategy for liver fibrosis.; 博士（医学）・甲第812号・令和4年3月15日; © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.; identifier:Journal of cellular and molecular medicine Vol.25 No.8 p.4001-4013 (2021 Apr); identifier:15821838; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3995; identifier:Journal of cellular and molecular medicine Vol. No. p.- (2021 Apr), 25(8): 4001-4013
• 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）: 10.1111/jcmm.16363
• 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/10564/3995/1/01%e7%94%b2812%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/10564/3995/2/02%e7%94%b2812%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3995/3/03%e7%94%b2812%e6%9c%ac%e6%96%87.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3995/4/04%e7%94%b2812Suppl..pdf fulltext