Blockade of platelet-derived growth factor receptor-β, not receptor-α ameliorates bleomycin-induced pulmonary fibrosis in mice

• Material Type: 博士論文
• Title: Blockade of platelet-derived growth factor receptor-β, not receptor-α ameliorates bleomycin-induced pulmonary fibrosis in mice
• Author/Editor: Kishi, Masami; Aono, Yoshinori; Satou, Seidai; Koyama, Kazuya; Azuma, Momoyo; Abe, Shuichi; Kawano, Hiroshi; Kishi, Jun; Toyoda, Yuko; Okazaki, Hiroyasu; Ogawa, Hirohisa; Uehara, Hisanori; Nishioka, Yasuhiko
• Author Heading: Kishi, Masami; Aono, Yoshinori; Satou, Seidai; Koyama, Kazuya; Azuma, Momoyo; Abe, Shuichi; Kawano, Hiroshi; Kishi, Jun; Toyoda, Yuko; Okazaki, Hiroyasu; Ogawa, Hirohisa; Uehara, Hisanori; Nishioka, Yasuhiko
• Publication, Distribution, etc.: PLOS
• Publication Date: 2018-12-31
• Publication Date (W3CDTF): 2018-12-31
• Alternative Title: 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
• Periodical title: PLOS ONE
• No. or year of volume/issue: 13 12
• Volume: 13
• Issue: 12
• Pages: e0209786-
• ISSN (Periodical Title): ISSN : 1932-6203
• Degree grantor/type: 徳島大学
• Date Granted: 2019-02-06
• Dissertation Number: 甲第3251号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Fibroblast; platelet-derived growth factor; pulmonary fibrosis
• Target Audience: 一般
• Note (General): 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.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): © 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.
• Related Material (DOI): 10.1371/journal.pone.0209786
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

Table of Contents

http://repo.lib.tokushima-u.ac.jp/files/public/11/113268/20190422105241734706/k3251_abstract_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/113268/20190422105242219658/k3251_fulltext.pdf fulltext