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 |
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タイトル |
Suppression of plasminogen activator inhibitor-1 by RNA interference attenuates pulmonary fibrosis |
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言語 |
en |
作成者 |
Senoo, Tadashi
Hattori, Noboru
Tanimoto, Takuya
Furonaka, Makoto
Ishikawa, Nobuhisa
Fujitaka, Kazunori
Haruta, Yoshinori
Murai, Hiroshi
Yokoyama, Akihito
Kohno, Nobuoki
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アクセス権 |
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アクセス権 |
open access |
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アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
権利情報 |
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権利情報 |
Copyright (c) 2010 BMJ Publishing Group & British Thoracic Society |
主題 |
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主題Scheme |
NDC |
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主題 |
490 |
内容記述 |
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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. |
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言語 |
en |
出版者 |
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出版者 |
BMJ Publishing Group |
言語 |
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言語 |
eng |
資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
出版タイプ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
10.1136/thx.2009.119974 |
関連情報 |
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識別子タイプ |
DOI |
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関連識別子 |
http://dx.doi.org/10.1136/thx.2009.119974 |
収録物識別子 |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
0040-6376 |
収録物識別子 |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA00863090 |
開始ページ |
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開始ページ |
334 |
書誌情報 |
Thorax
Thorax
巻 65,
号 4,
p. 334-340,
発行日 2010
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旧ID |
30125 |