Lipopolysaccharide Activates Toll-Like Receptor 4 and Prevents Cardiac Fibroblast-to-Myofibroblast Differentiation.
Cardiovasc Toxicol
; 17(4): 458-470, 2017 Oct.
Article
em En
| MEDLINE
| ID: mdl-28220374
ABSTRACT
Bacterial lipopolysaccharide (LPS) is a known ligand of Toll-like receptor 4 (TLR4) which is expressed in cardiac fibroblasts (CF). Differentiation of CF to cardiac myofibroblasts (CMF) is induced by transforming growth factor-ß1 (TGF-ß1), increasing alpha-smooth muscle actin (α-SMA) expression. In endothelial cells, an antagonist effect between LPS-induced signaling and canonical TGF-ß1 signaling was described; however, it has not been studied whether in CF and CMF the expression of α-SMA induced by TGF-ß1 is antagonized by LPS and the mechanism involved. In adult rat CF and CMF, α-SMA, ERK1/2, Akt, NF-κß, Smad3, and Smad7 protein levels were determined by western blot, TGF-ß isoforms by ELISA, and α-SMA stress fibers by immunocytochemistry. CF and CMF secrete the three TGF-ß isoforms, and the secretion levels of TGF-ß2 was affected by LPS treatment. In CF, LPS treatment decreased the protein levels of α-SMA, and this effect was prevented by TAK-242 (TLR4 inhibitor) and LY294002 (Akt inhibitor), but not by BAY 11-7082 (NF-κß inhibitor) and PD98059 (ERK1/2 inhibitor). TGF-ß1 increased α-SMA protein levels in CF, and LPS prevented partially this effect. In addition, in CMF α-SMA protein levels were decreased by LPS treatment, which was abolished by TAK-242. Finally, in CF LPS decreased the p-Smad3 phosphorylation and increased the Smad7 protein levels. LPS treatment prevents the CF-to-CMF differentiation and reverses the CMF phenotype induced by TGF-ß1, through decreasing p-Smad3 and increasing Smad7 protein levels.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Lipopolissacarídeos
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Miócitos Cardíacos
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Receptor 4 Toll-Like
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Miofibroblastos
Limite:
Animals
Idioma:
En
Revista:
Cardiovasc Toxicol
Assunto da revista:
ANGIOLOGIA
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CARDIOLOGIA
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TOXICOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Chile