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Significance of nuclear LOXL2 inhibition in fibroblasts and myofibroblasts in the fibrotic process of acute respiratory distress syndrome
http://hdl.handle.net/10458/0002000167
http://hdl.handle.net/10458/000200016766655cff-7545-40da-b94b-56406dd5e1e2
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
本文 (8.8 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2023-10-27 | |||||
| タイトル | ||||||
| タイトル | Significance of nuclear LOXL2 inhibition in fibroblasts and myofibroblasts in the fibrotic process of acute respiratory distress syndrome | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Lysyl oxidase-like 2 | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Nucleus | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Myofibroblast | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Snail | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Acute respiratory distress syndrome | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Fibrotic scaring | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
松尾, 彩子
× 松尾, 彩子× Tanida, Ryota× 柳, 重久× 坪内, 拡伸× 三浦, 綾子× Shigekusa, Takafumi× 松元, 信弘× 中里, 雅光 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Fibrotic scarring is an important prognostic factor of acute respiratory distress syndrome (ARDS). There are currently no antifibrotic drugs or other therapeutic agents for ARDS. Lysyl oxidase-like 2 (LOXL2), an amine oxidase, contributes to fibrotic scarring by facilitating collagen cross-linking. Recent clinical trials revealed that a monoclonal inhibitory antibody against LOXL2 failed to show benefit over placebo in patients with fibrotic disorders involving the lungs. These clinical results raise the possibility that targeting the extracellular enzymic activity of LOXL2 is not in itself sufficient to prevent fibrotic scarring. We investigated the role of LOXL2 in the pathogenesis of ARDS in vivo, in vitro, and in samples from patients with ARDS. After lung injury, LOXL2 was unevenly expressed in the nuclei of lung fibroblasts and myofibroblasts in the fibrotic phase. Nuclear LOXL2 expression was upregulated in lung fibroblasts after transforming growth factor-beta1 (TGF-β1)-treatment. LOXL2 silencing abrogated the TGF-β1-induced expression of a myofibrogenic-progenitor marker, the appearance of proto-myofibroblasts, and the evolution of differentiated myofibroblasts in lung fibroblasts. Nuclear upregulation of Snail was evident in myofibroblasts during the fibrotic phase after lung injury. We detected high levels of LOXL2 protein in the lungs of ARDS patients, specifically during the proliferative and fibrotic phases. Our results highlight nuclear LOXL2 in fibroblasts as a primary causative driver of cell-fate decision toward myofibroblasts and of the progression of fibrotic scarring. A nuclear-LOXL2-targeted agent could be a promising therapeutic strategy against fibrotic disorders including ARDS. | |||||
| 言語 | en | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Citation: Matsuo A, Tanida R, Yanagi S, Tsubouchi H, Miura A, Shigekusa T, Matsumoto N, Nakazato M. Significance of nuclear LOXL2 inhibition in fibroblasts and myofibroblasts in the fibrotic process of acute respiratory distress syndrome. Eur J Pharmacol. 2021 Feb 5;892:173754. doi: 10.1016/j.ejphar.2020.173754. Epub 2020 Nov 25. PMID: 33248114. |
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| 言語 | en | |||||
| 書誌情報 |
en : European Journal of Pharmacology 巻 892, p. 173754, 発行日 2021-02-05 |
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| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| 言語 | en | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 00142999 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1016/j.ejphar.2020.173754 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | © 2020 The Authors. Published by Elsevier B.V. | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
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松尾, 彩子, Tanida, Ryota, 柳, 重久, 坪内, 拡伸, 三浦, 綾子, Shigekusa, Takafumi, 松元, 信弘, 中里, 雅光, 2021, Significance of nuclear LOXL2 inhibition in fibroblasts and myofibroblasts in the fibrotic process of acute respiratory distress syndrome: Elsevier, 173754– p.
