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著作: Murakami Shinsuke/Nagaya Noritoshi/Itoh Takefumi/Kataoka Masaharu/[岩瀬 俊]/Horio Takeshi/Miyahara Yoshinori/Sakai Yoshiki/[寒川 賢治]/Kimura Hiroshi/Prostacyclin agonist with thromboxane synthase inhibitory activity (ONO-1301) attenuates bleomycin-induced pulmonary fibrosis in mice/[American Journal of Physiology. Lung Cellular and Molecular Physiology]

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163976
EOID
849203
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2017年3月6日(月) 13:35:11
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三木 ちひろ
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[科長]/[徳島大学.病院.診療科.内科]
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種別 必須 学術論文(審査論文)
言語 必須 英語
招待 推奨
審査 推奨 Peer Review
カテゴリ 推奨 研究
共著種別 推奨
学究種別 推奨
組織 推奨
著者 必須
  1. (英) Murakami Shinsuke
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. (英) Nagaya Noritoshi
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Itoh Takefumi
    役割 任意
    貢献度 任意
    学籍番号 推奨
  4. (英) Kataoka Masaharu
    役割 任意
    貢献度 任意
    学籍番号 推奨
  5. 岩瀬 俊
    役割 任意
    貢献度 任意
    学籍番号 推奨
  6. (英) Horio Takeshi
    役割 任意
    貢献度 任意
    学籍番号 推奨
  7. (英) Miyahara Yoshinori
    役割 任意
    貢献度 任意
    学籍番号 推奨
  8. (英) Sakai Yoshiki
    役割 任意
    貢献度 任意
    学籍番号 推奨
  9. 寒川 賢治(国立循環器病センター研究所)
    役割 任意
    貢献度 任意
    学籍番号 推奨
  10. (英) Kimura Hiroshi
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Prostacyclin agonist with thromboxane synthase inhibitory activity (ONO-1301) attenuates bleomycin-induced pulmonary fibrosis in mice

副題 任意
要約 任意

(英) The balance between prostacyclin and thromboxane A2 (TXA2) plays an important role in pulmonary homeostasis. However, little information is available regarding the therapeutic potency of these prostanoids for pulmonary fibrosis. We have recently developed ONO-1301, a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. Thus we investigated whether repeated administration of ONO-1301 attenuates bleomycin-induced pulmonary fibrosis in mice. After intratracheal injection of bleomycin or saline, mice were randomized to receive repeated subcutaneous administration of ONO-1301 or vehicle. Bronchoalveolar lavage (BAL) and histological analyses were performed at 3, 7, and 14 days after bleomycin injection. In vitro studies using mouse lung fibroblasts were also performed. ONO-1301 significantly attenuated the development of bleomycin-induced pulmonary fibrosis, as indicated by significant decreases in Ashcroft score and lung hydroxyproline content. ONO-1301 significantly reduced total cell count, neutrophil count, and total protein level in BAL fluid in association with a marked reduction of TXB2. A single administration of ONO-1301 significantly increased plasma cAMP level for >2 h. In vitro, ONO-1301 and a cAMP analog dose-dependently reduced cell proliferation in mouse lung fibroblasts. The reduction in cell proliferation by ONO-1301 was attenuated by a protein kinase A (PKA) inhibitor. Furthermore, bleomycin mice treated with ONO-1301 had a significantly higher survival rate than those given vehicle. These results suggest that repeated administration of ONO-1301 attenuates the development of bleomycin-induced pulmonary fibrosis and improves survival in bleomycin mice, at least in part by inhibition of TXA2 synthesis and activation of the cAMP/PKA pathway.

キーワード 推奨
  1. (英) adenosine 3',5'-cyclic monophosphate
  2. (英) fibroblast
  3. (英) neutrophil
  4. 線量生存率曲線(dose-survival curve)
発行所 推奨
誌名 必須 American Journal of Physiology. Lung Cellular and Molecular Physiology([アメリカ生理学会])
(pISSN: 1040-0605, eISSN: 1522-1504)
ISSN 任意 1040-0605
ISSN: 1040-0605 (pISSN: 1040-0605, eISSN: 1522-1504)
Title: American journal of physiology. Lung cellular and molecular physiology
Title(ISO): Am J Physiol Lung Cell Mol Physiol
Publisher: American Physiological Society
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 290
必須 1
必須 L59 L65
都市 任意
年月日 必須 2006年 1月 初日
URL 任意 http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16155090
DOI 任意 10.1152/ajplung.00042.2005    (→Scopusで検索)
PMID 任意 16155090    (→Scopusで検索)
CRID 任意
WOS 任意 000233897700008
Scopus 任意 2-s2.0-33644750037
評価値 任意
被引用数 任意 2
指導教員 推奨
備考 任意
  1. (英) Article.Affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, Osaka 565-8565, Japan.

  2. (英) Article.PublicationTypeList.PublicationType: Journal Article

  3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't