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ID 113268
タイトル別表記
PDGFレセプターαではなくβの阻害がマウスにおけるブレオマイシン誘発肺線維症を改善する
Role of platelet-derived growth factor receptor-α and -β in pulmonary fibrosis in mice
著者
岸, 昌美 徳島大学大学院医科学教育部(医学専攻)
Abe, Shuichi Tokushima University
Okazaki, Hiroyasu Tokushima University
キーワード
Fibroblast
platelet-derived growth factor
pulmonary fibrosis
資料タイプ
学位論文
抄録
Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of pulmonary fibrosis. Nintedanib, a multi-kinase inhibitor that targets several tyrosine kinases, including PDGF receptor (PDGFR), was recently approved as an anti-fibrotic agent to reduce the deterioration of FVC in patients with idiopathic pulmonary fibrosis (IPF). However, the effects of PDGFR-α or -β on pulmonary fibrosis remain unclear. In an attempt to clarify their effects, we herein used blocking antibodies specific for PDGFR-α (APA5) and -β (APB5) in a bleomycin (BLM)-induced pulmonary fibrosis mouse model. The effects of these treatments on the growth of lung fibroblasts were examined using the 3H-thymidine incorporation assay in vitro. The anti-fibrotic effects of these antibodies were investigated with the Ashcroft score and collagen content of lungs treated with BLM. Their effects on inflammatory cells in the lungs were also analyzed using bronchoalveolar lavage fluid. We investigated damage to epithelial cells and the proliferation of fibroblasts in the lungs. APA5 and APB5 inhibited the phosphorylation of PDGFR-α and -β as well as the proliferation of lung fibroblasts induced by PDGF-AA and BB. The administration of APB5, but not APA5 effectively inhibited BLM-induced pulmonary fibrosis in mice. Apoptosis and the proliferation of epithelial cells and fibroblasts were significantly decreased by the treatment with APB5, but not by APA5. The late treatment with APB5 also ameliorated fibrosis in lungs treated with BLM. These results suggest that PDGFR-α and -β exert different effects on BLM-induced pulmonary fibrosis in mice. A specific approach using the blocking antibody for PDGFR-β may be useful for the treatment of pulmonary fibrosis.
掲載誌名
PLOS ONE
ISSN
19326203
出版者
PLOS
13
12
開始ページ
e0209786
発行日
2018-12-31
備考
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Masami Kishiの学位論文として提出され, 学位審査・授与の対象となっている。
権利情報
© 2018 Kishi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3251号
学位記番号
甲医第1400号
学位授与年月日
2019-02-06
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系