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Suppression of plasminogen activator inhibitor-1 by RNA interference attenuates pulmonary fibrosis

https://hiroshima.repo.nii.ac.jp/records/2008979
https://hiroshima.repo.nii.ac.jp/records/2008979
7aee52c8-e636-4e03-8231-d82aff719b74
名前 / ファイル ライセンス アクション
Thorax_65_334.pdf Thorax_65_334.pdf (1.1 MB)
Item type デフォルトアイテムタイプ_(フル)(1)
公開日 2023-03-18
タイトル
タイトル Suppression of plasminogen activator inhibitor-1 by RNA interference attenuates pulmonary fibrosis
言語 en
作成者 Senoo, Tadashi

× Senoo, Tadashi

en Senoo, Tadashi

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Hattori, Noboru

× Hattori, Noboru

en Hattori, Noboru

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Tanimoto, Takuya

× Tanimoto, Takuya

en Tanimoto, Takuya

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Furonaka, Makoto

× Furonaka, Makoto

en Furonaka, Makoto

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Ishikawa, Nobuhisa

× Ishikawa, Nobuhisa

en Ishikawa, Nobuhisa

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Fujitaka, Kazunori

× Fujitaka, Kazunori

en Fujitaka, Kazunori

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Haruta, Yoshinori

× Haruta, Yoshinori

en Haruta, Yoshinori

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Murai, Hiroshi

× Murai, Hiroshi

en Murai, Hiroshi

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Yokoyama, Akihito

× Yokoyama, Akihito

en Yokoyama, Akihito

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Kohno, Nobuoki

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en Kohno, Nobuoki

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アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
権利情報
権利情報 Copyright (c) 2010 BMJ Publishing Group & British Thoracic Society
主題
主題Scheme NDC
主題 490
内容記述
内容記述 Background and aim: There is a growing body of evidence demonstrating that plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. In fact, PAI-1 knockout mice are protected from bleomycin-induced pulmonary fibrosis. This study was conducted to determine whether the intrapulmonary administration of small interfering RNA (siRNA) targeting PAI-1 (PAI-1-siRNA) limits the development of bleomycin-induced pulmonary fibrosis. Methods: Lung biopsies from patients with idiopathic pulmonary fibrosis (IPF) were stained for PAI-1. The distribution of siRNA in the lung, the PAI-1 level in bronchoalveolar (BAL) fluid and the extent of fibrotic changes in the lung were evaluated following the intranasal administration of PAI-1-siRNA in a mouse model of bleomycin-induced pulmonary fibrosis. The effect of PAI-1-siRNA on the epithelial to mesenchymal transition (EMT) was also evaluated using a mouse lung epithelial cell line, LA-4. Results: PAI-1 was overexpressed in the hyperplastic type 2 pneumocytes lining the honeycomb lesions of patients with IPF. The single intranasal instillation of PAI-1-siRNA resulted in the diffuse uptake of siRNA into the epithelial cells lining the dense fibrotic lesions. The repeated administration of PAI-1-siRNA initiated during either the inflammatory or the fibrotic phase into bleomycin-injured mice reduced the PAI-1 level in BAL fluid and limited the accumulation of collagen in the lungs. EMT induced by transforming growth factor β (TGFβ) in LA-4 cells was inhibited by transfection with PAI-1-siRNA. Conclusions: The direct suppression of PAI-1 in the lung by the intrapulmonary administration of PAI-1-siRNA attenuated the development and progression of pulmonary fibrosis. The inhibition of EMT may be, at least in part, involved in this effect.
言語 en
出版者
出版者 BMJ Publishing Group
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
出版タイプ
出版タイプ VoR
出版タイプResource http://purl.org/coar/version/c_970fb48d4fbd8a85
関連情報
識別子タイプ DOI
関連識別子 10.1136/thx.2009.119974
関連情報
識別子タイプ DOI
関連識別子 http://dx.doi.org/10.1136/thx.2009.119974
収録物識別子
収録物識別子タイプ ISSN
収録物識別子 0040-6376
収録物識別子
収録物識別子タイプ NCID
収録物識別子 AA00863090
開始ページ
開始ページ 334
書誌情報 Thorax
Thorax

巻 65, 号 4, p. 334-340, 発行日 2010
旧ID 30125
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