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Metformin reduces pleural fibroelastosis by inhibition of extracellular matrix production induced by CD90-positive myofibroblasts
http://hdl.handle.net/10271/00004212
http://hdl.handle.net/10271/000042123d1c6d39-344d-4148-a8d9-ece794defe1c
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
論文本文 (10.7 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||
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| 公開日 | 2022-11-29 | |||||||
| タイトル | ||||||||
| タイトル | Metformin reduces pleural fibroelastosis by inhibition of extracellular matrix production induced by CD90-positive myofibroblasts | |||||||
| 言語 | en | |||||||
| 言語 | ||||||||
| 言語 | eng | |||||||
| キーワード | ||||||||
| 主題 | Metformin | |||||||
| キーワード | ||||||||
| 主題 | myofibroblast | |||||||
| キーワード | ||||||||
| 主題 | pleural fibrosis | |||||||
| キーワード | ||||||||
| 主題 | pleuroparenchymal fibroelastosis | |||||||
| 資源タイプ | ||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||
| 資源タイプ | doctoral thesis | |||||||
| アクセス権 | ||||||||
| アクセス権 | open access | |||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||
| その他のタイトル | ||||||||
| その他のタイトル | 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 | |||||||
| 著者 |
青島, 洋一郎
× 青島, 洋一郎
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| 書誌情報 |
en : American Journal of Translational Research 巻 13, 号 11, p. 12318-12337, 発行日 2021-11-30 |
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| 出版者 | ||||||||
| 出版者 | e-Century Publishing | |||||||
| 言語 | en | |||||||
| 抄録 | ||||||||
| 内容記述タイプ | Abstract | |||||||
| 内容記述 | 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. | |||||||
| 言語 | en | |||||||
| 学位名 | ||||||||
| 学位名 | 博士（医学） | |||||||
| 学位の区分 | ||||||||
| 内容記述 | doctoral | |||||||
| 学位の分野 | ||||||||
| 内容記述 | 医学系研究科 | |||||||
| 学位授与機関 | ||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||
| 学位授与機関識別子 | 13802 | |||||||
| 学位授与機関名 | 浜松医科大学 | |||||||
| 学位授与年月日 | ||||||||
| 学位授与年月日 | 2022-03-14 | |||||||
| 学位授与番号 | ||||||||
| 学位授与番号 | 甲第894号 | |||||||
| EISSN | ||||||||
| 収録物識別子タイプ | EISSN | |||||||
| 収録物識別子 | 1943-8141 | |||||||
| PubMed番号 | ||||||||
| 識別子タイプ | PMID | |||||||
| 関連識別子 | 34956455 | |||||||
| 著者版フラグ | ||||||||
| 出版タイプ | VoR | |||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||
