Lipopolysaccharide Activates Toll-Like Receptor 4 and Prevents Cardiac Fibroblast-to-Myofibroblast Differentiation

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dc.contributor.authorBolivar, Samir
dc.contributor.authorSantana, Roxana
dc.contributor.authorAyala, Pedro
dc.contributor.authorLandaeta, Rodolfo
dc.contributor.authorBoza, Pia
dc.contributor.authorHumeres, Claudio
dc.contributor.authorVivar, Raul
dc.contributor.authorMunoz, Claudia
dc.contributor.authorPardo, Viviana
dc.contributor.authorFernandez, Samuel
dc.contributor.authorAnfossi, Renatto
dc.contributor.authorDiaz Araya, Guillermo
dc.date.accessioned2024-01-10T13:50:00Z
dc.date.available2024-01-10T13:50:00Z
dc.date.issued2017
dc.description.abstractBacterial 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-beta 1 (TGF-beta 1), increasing alpha-smooth muscle actin (alpha-SMA) expression. In endothelial cells, an antagonist effect between LPS-induced signaling and canonical TGF-beta 1 signaling was described; however, it has not been studied whether in CF and CMF the expression of alpha-SMA induced by TGF-beta 1 is antagonized by LPS and the mechanism involved. In adult rat CF and CMF, alpha-SMA, ERK1/2, Akt, NF-kappa beta, Smad3, and Smad7 protein levels were determined by western blot, TGF-beta isoforms by ELISA, and alpha-SMA stress fibers by immunocytochemistry. CF and CMF secrete the three TGF-beta isoforms, and the secretion levels of TGF-beta 2 was affected by LPS treatment. In CF, LPS treatment decreased the protein levels of alpha-SMA, and this effect was prevented by TAK-242 (TLR4 inhibitor) and LY294002 (Akt inhibitor), but not by BAY 11-7082 (NF-kappa beta inhibitor) and PD98059 (ERK1/2 inhibitor). TGF-beta 1 increased alpha-SMA protein levels in CF, and LPS prevented partially this effect. In addition, in CMF alpha-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-beta 1, through decreasing p-Smad3 and increasing Smad7 protein levels.
dc.description.funderFONDECYT
dc.description.funderCONICYT
dc.fechaingreso.objetodigital2024-03-14
dc.format.extent13 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1007/s12012-017-9404-4
dc.identifier.eissn1559-0259
dc.identifier.issn1530-7905
dc.identifier.pubmedidMEDLINE:28220374
dc.identifier.urihttps://doi.org/10.1007/s12012-017-9404-4
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/79498
dc.identifier.wosidWOS:000411104600010
dc.information.autorucMedicina; Ayala P;S/I;1013060
dc.issue.numero4
dc.language.isoen
dc.nota.accesoContenido parcial
dc.pagina.final470
dc.pagina.inicio458
dc.publisherHUMANA PRESS INC
dc.revistaCARDIOVASCULAR TOXICOLOGY
dc.rightsacceso restringido
dc.subjectLipopolysaccharide
dc.subjectTLR4
dc.subjectCardiac fibroblast
dc.subjectalpha-SMA
dc.subjectMUSCLE ACTIN EXPRESSION
dc.subjectTGF-BETA RECEPTOR
dc.subjectEXTRACELLULAR-MATRIX
dc.subjectSMAD7
dc.subjectCELLS
dc.subjectFIBROSIS
dc.subjectTLR4
dc.subjectINTERACTS
dc.subjectMECHANISM
dc.subjectAPOPTOSIS
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleLipopolysaccharide Activates Toll-Like Receptor 4 and Prevents Cardiac Fibroblast-to-Myofibroblast Differentiation
dc.typeartículo
dc.volumen17
sipa.codpersvinculados1013060
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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