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Please use this identifier to cite or link to this item: http://ir.fmu.ac.jp/dspace/handle/123456789/654

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Title: 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
Authors: Ono, Yuko
Sakamoto, Kazuho
Affiliation: 救急医療学講座
薬理学講座
Source title: PLoS One
Volume: 12
Issue: 7
Start page: e0182040
Issue Date: 24-Jul-2017
Abstract: 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
Publisher: Public Library of Science
language: eng
URI: http://ir.fmu.ac.jp/dspace/handle/123456789/654
Full text 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 ID: 28742154
Related Page: https://doi.org/10.1371/journal.pone.0182040
Rights: © 2017 Ono, Sakamoto. This is an open access article distributed under the terms of the Creative Commons Attribution License.
Rights: http://creativecommons.org/licenses/by/4.0/
Appears in Collections:a10 学術雑誌論文等 = Journal Article

Files in This Item:

File Description SizeFormat
PLoSOne_12_e0182040.pdf18.47 MBAdobe PDFDownload
S1Data.xlsxExcel spreadsheet providing the raw data for each figure.79.29 kBMicrosoft ExcelDownload

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