Metformin reduces pleural fibroelastosis by inhibition of extracellular matrix production induced by CD90-positive myofibroblasts

• Material Type: 博士論文
• Title: Metformin reduces pleural fibroelastosis by inhibition of extracellular matrix production induced by CD90-positive myofibroblasts
• Author/Editor: 青島, 洋一郎
• Author Heading: 青島, 洋一郎
• Publication, Distribution, etc.: e-Century Publishing
• Publication Date: 2021-11-30
• Publication Date (W3CDTF): 2021-11-30
• Alternative Title: メトホルミンは、CD90陽性筋線維芽細胞によって引き起こされる細胞外マトリックス産生を阻害することにより胸膜線維弾性症を軽減する
• Degree grantor/type: 浜松医科大学
• Date Granted: 2022-03-14
• Date Granted (W3CDTF): 2022-03-14
• Dissertation Number: 甲第894号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Metformin; myofibroblast; pleural fibrosis; pleuroparenchymal fibroelastosis
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; Metformin, an AMP-activated protein kinase activator used to treat diabetes mellitus, has recently attracted attention as a promising anti-fibrotic agent. However, its anti-fibrotic effects on pleural fibroelastosis remain unknown. We induced mouse pleural fibroelastosis by intra-pleural coadministration of bleomycin and carbon and evaluated its validity as a preclinical model for human pleural fibrosis. We assessed the expression of the myofibroblast surface marker CD90 in the fibrotic pleura and the effects of metformin in vivo and in vitro. Finally, we evaluated the effects of metformin on human pleural mesothelial cells stimulated by transforming growth factor β1 (TGFβ1). The fibrotic pleura in mice had collagen and elastin fiber deposition similar to that seen in human fibrotic pleura. Moreover, CD90-positive myofibroblasts were detected in and successfully isolated from the fibrotic pleura. Metformin significantly suppressed the deposition of collagen and elastic fibers in the fibrotic pleura and decreased the expression of extracellular matrix (ECM)-related genes, including Col1a1, Col3a1, Fn1, and Eln, in pleural CD90-positive myofibroblasts. In human pleural mesothelial cells, metformin decreased TGFβ1-induced upregulation of ECM-related genes and SNAI1. Overall, metformin suppresses pleural fibroelastosis by inhibition of ECM production by pleural myofibroblasts, suggesting that this drug has therapeutic potential against human pleural fibrosis, including pleuroparenchymal fibroelastosis.
• Persistent ID (NDL): info:ndljp/pid/12651531; https://dl.ndl.go.jp/pid/12651531
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2023-03-02T11:18:10+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10271/00004212; https://hama-med.repo.nii.ac.jp/records/4090
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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