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ID 113268
Title Alternative
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
Author
Kishi, Masami Tokushima University
Abe, Shuichi Tokushima University
Okazaki, Hiroyasu Tokushima University
Keywords
Fibroblast
platelet-derived growth factor
pulmonary fibrosis
Content Type
Thesis or Dissertation
Description
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.
Journal Title
PLOS ONE
ISSN
19326203
Publisher
PLOS
Volume
13
Issue
12
Start Page
e0209786
Published Date
2018-12-31
Remark
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。
Rights
© 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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3251号
Diploma Number
甲医第1400号
Granted Date
2019-02-06
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences