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Identification of a Novel Deactivating Small-Molecule Compound for Fibrogenic Hepatic Stellate Cells
https://repository.lib.tottori-u.ac.jp/records/4721
https://repository.lib.tottori-u.ac.jp/records/472167e4b62c-03bb-4ee4-9670-2a57640f9a3f
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
yam63(1)_79.pdf (2.0 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 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 | ||||||
| 主題 | deactivation | |||||
| キーワード | ||||||
| 主題 | hepatic stellate cells | |||||
| キーワード | ||||||
| 主題 | liver fibrosis | |||||
| キーワード | ||||||
| 主題 | small-molecule compound | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | deactivation | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | hepatic stellate cells | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | liver fibrosis | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題 | small-molecule compound | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
Sakaguchi, Takuki
× Sakaguchi, Takuki× Kono, Yohei× Itaba, Noriko× Morimoto, Minoru× Isomoto, Hajime× Shiota, Goshi |
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| 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 | ||||||
| 値 | Original Article | |||||
| 出版者 | ||||||
| 出版者 | Tottori University Medical Press | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 05135710 | |||||
| 書誌レコードID | ||||||
| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA00892882 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.33160/yam.2020.02.013 | |||||
| 権利 | ||||||
| 権利情報 | Yonago Acta medica 編集委員会 | |||||
| 情報源 | ||||||
| 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 | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.jstage.jst.go.jp/article/yam/63/1/63_2020.02.013/_article/ | |||||
| 関連名称 | https://www.jstage.jst.go.jp/article/yam/63/1/63_2020.02.013/_article/ | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.lib.tottori-u.ac.jp/yam/yam/yam63-1/63-1contents.html | |||||
| 関連名称 | http://www.lib.tottori-u.ac.jp/yam/yam/yam63-1/63-1contents.html | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| EISSN | ||||||
| 値 | 1346-8049 | |||||
