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Transgenically-expressed secretoglobin 3A2 accelerates resolution of bleomycin-induced pulmonary fibrosis in mice

http://hdl.handle.net/10659/4973
http://hdl.handle.net/10659/4973
00324bd1-59f9-4c41-80fb-1bdbeae05426
名前 / ファイル ライセンス アクション
S-2016-150_okamoto.pdf S-2016-150_okamoto.pdf (4.0 MB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2017-06-09
タイトル
タイトル Transgenically-expressed secretoglobin 3A2 accelerates resolution of bleomycin-induced pulmonary fibrosis in mice
言語
言語 eng
キーワード
主題Scheme Other
主題 Secretoglobin
キーワード
主題Scheme Other
主題 SCGB
キーワード
主題Scheme Other
主題 SCGB3A2
キーワード
主題Scheme Other
主題 Bleomycin-induced pulmonary fibrosis model
キーワード
主題Scheme Other
主題 Spontaneous resolution of bleomycin-induced pulmonary fibrosis
キーワード
主題Scheme Other
主題 Transgenic mouse
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
著者 Cai, Yan

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Cai, Yan

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Yoneda, Mitsuhiro

× Yoneda, Mitsuhiro

WEKO 7509

Yoneda, Mitsuhiro

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Tomita, Takeshi

× Tomita, Takeshi

WEKO 7510

Tomita, Takeshi

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Kurotani, Reiko

× Kurotani, Reiko

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Kurotani, Reiko

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Okamoto, Minoru

× Okamoto, Minoru

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Okamoto, Minoru

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Kido, Taketomo

× Kido, Taketomo

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Kido, Taketomo

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Abe, Hiroyuki

× Abe, Hiroyuki

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Abe, Hiroyuki

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Mitzner, Wayne

× Mitzner, Wayne

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Mitzner, Wayne

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Guha, Arjun

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Guha, Arjun

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Kimura, Shioko

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Kimura, Shioko

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抄録
内容記述タイプ Abstract
内容記述 [Background] Secretoglobin (SCGB) 3A2, a cytokine-like secretory protein of small molecular weight, is predominantly expressed in airway epithelial cells. While SCGB3A2 is known to have anti-inflammatory, growth factor, and anti-fibrotic activities, whether SCGB3A2 has any other roles, particularly in lung homeostasis and disease has not been demonstrated in vivo. The aim of this study was to address these questions in mice. [Methods] A transgenic mouse line that expresses SCGB3A2 in the lung using the human surfactant protein-C promoter was established. Detailed histological, immunohistochemical, physiological, and molecular characterization of the Scgb3a2-transgenic mouse lungs were carried out. Scgb3a2-transgenic and wild-type mice were subjected to bleomycin-induced pulmonary fibrosis model, and their lungs and bronchoalveolar lavage fluids were collected at various time points during 9 weeks post-bleomycin treatment for further analysis. [Results] Adult Scgb3a2-transgenic mouse lungs expressed approximately five-fold higher levels of SCGB3A2 protein in comparison to wild-type mice as determined by western blotting of lung tissues. Immunohistochemistry showed that expression was localized to alveolar type II cells in addition to airway epithelial cells, thus accurately reflecting the site of surfactant protein-C expression. Scgb3a2-transgenic mice showed normal lung development and histology, and no overt gross phenotypes. However, when subjected to a bleomycin-induced pulmonary fibrosis model, they initially exhibited exacerbated fibrosis at 3 weeks post-bleomycin administration that was more rapidly resolved by 6 weeks as compared with wild-type mice, as determined by lung histology, Masson Trichrome staining and hydroxyproline content, inflammatory cell numbers, expression of collagen genes, and proinflammatory cytokine levels. The decrease of fibrosis coincided with the increased expression of SCGB3A2 in Scgb3a2-transgenic lungs. [Conclusions] These results demonstrate that SCGB3A2 is an anti-fibrotic agent, and suggest a possible therapeutic use of recombinant SCGB3A2 in the treatment of pulmonary fibrosis.
書誌情報 BMC Pulmonary Medicine

巻 15, p. 72-1-72-13, 発行日 2015-07
ISSN
収録物識別子タイプ ISSN
収録物識別子 1471-2466
DOI
関連タイプ isIdenticalTo
識別子タイプ DOI
関連識別子 10.1186/s12890-015-0065-4
権利
権利情報 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
権利
権利情報 © Cai et al. 2015
権利(URI)
権利情報 http://creativecommons.org/licenses/by/4.0 | http://creativecommons.org/licenses/by/4.0
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
出版者
出版者 BioMed Central Ltd
資源タイプ
内容記述タイプ Other
内容記述 Article
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