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福島県立医科大学学術成果リポジトリ = Fukushima Medical University Repository >
A 医学部 = School of Medicine >
a10 学術雑誌論文等 = Journal Article >
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http://ir.fmu.ac.jp/dspace/handle/123456789/654
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| タイトル: | Lipopolysaccharide inhibits myogenic differentiation of C2C12 myoblasts through the Toll-like receptor 4-nuclear factor-κB signaling pathway and myoblast-derived tumor necrosis factor-α |
| 著者: | Ono, Yuko
Sakamoto, Kazuho |
| 学内所属: | 救急医療学講座
薬理学講座 |
| 誌名/書名: | PLoS One |
| 巻: | 12 |
| 号: | 7 |
| 開始ページ: | e0182040 |
| 発行日: | 2017年7月24日 |
| 抄録: | Background: Circulating lipopolysaccharide (LPS) concentrations are often elevated in patients with sepsis or with various endogenous diseases that are associated with metabolic endotoxemia. Involuntary loss of skeletal muscle, termed muscle wasting, is commonly observed in these conditions, suggesting that circulating LPS might play an essential role in its development. Although impairment of muscle regeneration is an important determinant of skeletal muscle wasting, it is unclear whether LPS affects this process and, if so, by what mechanism. Here, we used the C2C12 myoblast cell line to investigate the effects of LPS on myogenesis. Methods: C2C12 myoblasts were grown to 80% confluence and induced to differentiate in the absence or presence of LPS (0.1 or 1 μg/mL); TAK-242 (1 μM), a specific inhibitor of Toll-like receptor 4 (TLR4) signaling; and a tumor necrosis factor (TNF)-α neutralizing antibody (5 μg/mL). Expression of a skeletal muscle differentiation marker (myosin heavy chain II), two essential myogenic regulatory factors (myogenin and MyoD), and a muscle negative regulatory factor (myostatin) was analyzed by western blotting. Nuclear factor-κB (NF-κB) DNA-binding activity was measured using an enzyme-linked immunosorbent assay. Results: LPS dose-dependently and significantly decreased the formation of multinucleated myotubes and the expression of myosin heavy chain II, myogenin, and MyoD, and increased NF-κB DNA-binding activity and myostatin expression. The inhibitory effect of LPS on myogenic differentiation was reversible, suggesting that it was not caused by nonspecific toxicity. Both TAK-242 and anti-TNF-α reduced the LPS-induced increase in NF-κB DNA-binding activity, downregulation of myogenic regulatory factors, and upregulation of myostatin, thereby partially rescuing the impairment of myogenesis. Conclusions: Our data suggest that LPS inhibits myogenic differentiation via a TLR4–NF-κB-dependent pathway and an autocrine/paracrine TNF-α-induced pathway. These pathways may be involved in the development of muscle wasting caused by sepsis or metabolic endotoxemia |
| 出版者: | Public Library of Science |
| 本文の言語: | eng |
| このページのURI: | http://ir.fmu.ac.jp/dspace/handle/123456789/654 |
| 本文URL: | http://ir.fmu.ac.jp/dspace/bitstream/123456789/654/1/PLoSOne_12_e0182040.pdf |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0182040 |
| PubMed番号: | 28742154 |
| 関連ページ: | https://doi.org/10.1371/journal.pone.0182040 |
| 権利情報: | © 2017 Ono, Sakamoto. This is an open access article distributed under the terms of the Creative Commons Attribution License. |
| 権利情報: | http://creativecommons.org/licenses/by/4.0/ |
| 出現コレクション: | a10 学術雑誌論文等 = Journal Article
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