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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3995

Title: Lenvatinib prevents liver fibrosis by inhibiting hepatic stellate cell activation and sinusoidal capillarization in experimental liver fibrosis.
Other Titles: 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。
Authors: Ogawa, Hiroyuki
Kaji, Kosuke
Nishimura, Norihisa
Takagi, Hirotetsu
Ishida, Koji
Takaya, Hiroaki
Kawaratani, Hideto
Moriya, Kei
Namisaki, Tadashi
Akahane, Takemi
Yoshiji, Hitoshi
Keywords: angiogenesis
hepatic stellate cell
lenvatinib
liver fibrosis
PDGF
VEGF
Issue Date: Apr-2021
Publisher: John Wiley & Sons
Citation: Journal of cellular and molecular medicine Vol.25 No.8 p.4001-4013 (2021 Apr)
Abstract: 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.
Description: 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.
URI: http://hdl.handle.net/10564/3995
ISSN: 15821838
Academic Degrees and number: 24601A812
Degree-granting date: 2022-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2021年度

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