Metformin reduces pleural fibroelastosis by inhibition of extracellular matrix production induced by CD90-positive myofibroblasts
AJTR Copyright © 2021..
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.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
American journal of translational research - 13(2021), 11 vom: 22., Seite 12318-12337 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Aoshima, Yoichiro [VerfasserIn] |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Revised 28.12.2021 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a myofibroblast | |
| 650 | 4 | |a pleural fibrosis | |
| 650 | 4 | |a pleuroparenchymal fibroelastosis | |
| 700 | 1 | |a Enomoto, Yasunori |e verfasserin |4 aut | |
| 700 | 1 | |a Fukada, Atsuki |e verfasserin |4 aut | |
| 700 | 1 | |a Kurita, Yuki |e verfasserin |4 aut | |
| 700 | 1 | |a Matsushima, Sayomi |e verfasserin |4 aut | |
| 700 | 1 | |a Meguro, Shiori |e verfasserin |4 aut | |
| 700 | 1 | |a Kosugi, Isao |e verfasserin |4 aut | |
| 700 | 1 | |a Kawasaki, Hideya |e verfasserin |4 aut | |
| 700 | 1 | |a Katsura, Hiroaki |e verfasserin |4 aut | |
| 700 | 1 | |a Fujisawa, Tomoyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Enomoto, Noriyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Nakamura, Yutaro |e verfasserin |4 aut | |
| 700 | 1 | |a Inui, Naoki |e verfasserin |4 aut | |
| 700 | 1 | |a Suda, Takafumi |e verfasserin |4 aut | |
| 700 | 1 | |a Iwashita, Toshihide |e verfasserin |4 aut | |
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