| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2020-02-28 |
| タイトル |
|
|
タイトル |
Identification of a Novel Deactivating Small-Molecule Compound for Fibrogenic Hepatic Stellate Cells |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
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主題Scheme |
Other |
|
主題 |
deactivation |
| キーワード |
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|
主題Scheme |
Other |
|
主題 |
hepatic stellate cells |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
liver fibrosis |
| キーワード |
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|
主題Scheme |
Other |
|
主題 |
small-molecule compound |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
deactivation |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
hepatic stellate cells |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
liver fibrosis |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
small-molecule compound |
| 資源タイプ |
|
|
資源タイプ |
journal article |
| 著者 |
Sakaguchi, Takuki
Kono, Yohei
Itaba, Noriko
Morimoto, Minoru
Isomoto, Hajime
Shiota, Goshi
|
| 著者所属（英） |
|
|
言語 |
en |
|
値 |
Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medical Sciences, Tottori University / Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine |
| 著者所属（英） |
|
|
言語 |
en |
|
値 |
Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medical Sciences, Tottori University |
| 著者所属（英） |
|
|
言語 |
en |
|
値 |
Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medical Sciences, Tottori University |
| 著者所属（英） |
|
|
言語 |
en |
|
値 |
Research Initiative Center, Tottori University |
| 著者所属（英） |
|
|
言語 |
en |
|
値 |
Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, School of Medicine, Tottori University Faculty of Medicine |
| 著者所属（英） |
|
|
言語 |
en |
|
値 |
Department of Genetic Medicine and Regenerative Therapeutics, Graduate School of Medical Sciences, Tottori University |
| 抄録 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
Background: Liver fibrosis progresses to decompensated liver cirrhosis, for which medical needs remain unmet. We recently developed IC-2, a small-molecule compound that suppresses Wnt/β-catenin signaling, and found that IC-2 also suppresses liver fibrosis. In this study, we performed three-step screening of newly synthesized IC-2 derivatives to identify other small-molecule compounds that suppress liver fibrosis. Methods: The screening system consisted of three steps: a cell viability assay, a transcription factor 4 (TCF4) reporter assay, and induction of α-smooth muscle actin (α-SMA) and collagen 1α1 (Col1A1) expression in response to each compound. Screening using human LX-2 hepatic stellate cells (HSCs) was performed to target HSCs, which are the driver cells of liver fibrosis. Results: In the first step, since 9b and 9b-CONH2 at 100 μM did not have any effects on cell viability, they were omitted in the next screening. Additionally, the conditions that led to > 40% inhibition of the controls were also excluded in subsequent screening. The second step was performed under 31 conditions for 19 small-molecule compounds. Sixteen small-molecule compounds caused significant reduction of TCF4 activity relative to that of 0.1% DMSO. Of the 16 compounds, the 10 showing the greatest suppression of TCF4 activity were selected for the third step. Expressions of mRNA for α-SMA and Col1A1 were significantly reduced by seven and three small-molecule compounds, respectively. The greatest reductions in the α-SMA and Col1A1 mRNA expressions were observed in the cells treated with IC-2-F. Protein expressions of α-SMA and Col1A1 caused by IC-2-F were also comparable to those caused by IC-2. Conclusion: IC-2-F was identified as a novel deactivating small-molecule compound for HSCs in vitro. These data suggest that IC-2-F is a promising medicine for liver fibrosis. |
| 書誌情報 |
Yonago Acta Medica
en : Yonago Acta Medica
巻 63,
号 1,
p. 79-87,
発行日 2020-02-20
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| 雑誌内区分 |
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値 |
Original Article |
| 出版者 |
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出版者 |
Tottori University Medical Press |
| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
05135710 |
| 書誌レコードID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA00892882 |
| DOI |
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|
関連タイプ |
isIdenticalTo |
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|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.33160/yam.2020.02.013 |
| 権利 |
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|
権利情報 |
Yonago Acta medica 編集委員会 |
| 情報源 |
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|
関連名称 |
Takuki Sakaguchi, Yohei Kono, Noriko Itaba, Minoru Morimoto, Hajime Isomoto, Goshi Shiota, Identification of a Novel Deactivating Small-Molecule Compound for Fibrogenic Hepatic Stellate Cells, Yonago Acta Medica, 2020, Volume 63, Issue 1, Pages 79-87, Rel |
| 関連サイト |
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|
識別子タイプ |
URI |
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関連識別子 |
https://www.jstage.jst.go.jp/article/yam/63/1/63_2020.02.013/_article/ |
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関連名称 |
https://www.jstage.jst.go.jp/article/yam/63/1/63_2020.02.013/_article/ |
| 関連サイト |
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識別子タイプ |
URI |
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関連識別子 |
http://www.lib.tottori-u.ac.jp/yam/yam/yam63-1/63-1contents.html |
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関連名称 |
http://www.lib.tottori-u.ac.jp/yam/yam/yam63-1/63-1contents.html |
| 著者版フラグ |
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出版タイプ |
VoR |
| EISSN |
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値 |
1346-8049 |
yam63(1)_79.pdf (2.0 MB)
