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Authordc.contributor.authorGarcía Miguel, Marina 
Authordc.contributor.authorRiquelme, Jaime A. 
Authordc.contributor.authorNorambuena Soto, Ignacio 
Authordc.contributor.authorMorales, Pablo E. 
Authordc.contributor.authorSanhueza Olivares, Fernanda 
Authordc.contributor.authorNúñez Soto, Constanza Belén 
Authordc.contributor.authorMondaca Ruff, David 
Authordc.contributor.authorCancino Arenas, Nicole 
Authordc.contributor.authorSan Martín, Alejandra 
Authordc.contributor.authorChiong Lay, Mario 
Cita de ítemdc.identifier.citationPLoS one 13(5): e0197210es_ES
Abstractdc.description.abstractVascular smooth muscle cells (VSMC) dedifferentiation from a contractile to a synthetic phenotype contributes to atherosclerosis. Atherosclerotic tissue has a chronic inflammatory component with high levels of tumor necrosis factor-alpha (TNF-alpha). VSMC of atheromatous plaques have increased autophagy, a mechanism responsible for protein and intracellular organelle degradation. The aim of this study was to evaluate whether TNF-alpha induces phenotype switching of VSMCs and whether this effect depends on autophagy. Rat aortic Vascular smooth A7r5 cell line was used as a model to examine the phenotype switching and autophagy. These cells were stimulated with TNF-alpha 100 ng/mL. Autophagy was determined by measuring LC3-II and p62 protein levels. Autophagy was inhibited using chloroquine and siRNA Beclin1. Cell dedifferentiation was evaluated by measuring the expression of contractile proteins alpha-SMA and SM22, extracellular matrix protein osteopontin and type I collagen levels. Cell proliferation was measured by [H-3]-thymidine incorporation and MTT assay, and migration was evaluated by wound healing and transwell assays. Expression of IL-1 beta, IL-6 and IL-10 was assessed by ELISA. TNF-alpha induced autophagy as determined by increased LC3-II (1.91 +/- 0.21, p<0.001) and decreased p62 (0.86 +/- 0.02, p<0.05) when compared to control. Additionally, TNF-alpha decreased alpha-SMA (0.74 +/- 0.12, p<0.05) and SM22 (0.54 +/- 0.01, p<0.01) protein levels. Consequently, TNF-alpha induced migration (1.25 +/- 0.05, p<0.05), proliferation (2.33 +/- 0.24, p<0.05), and the secretion of IL-6 (258 +/- 53, p<0.01), type I collagen (3.09 +/- 0.85, p<0.01) and osteopontin (2.32 +/- 0.46, p<0.01). Inhibition of autophagy prevented all the TNF-alpha-induced phenotypic changes. TNF-alpha induces phenotype switching in A7r5 cell line by a mechanism that required autophagy. Therefore, autophagy may be a potential therapeutic target for the treatment of atherosclerosis.es_ES
Patrocinadordc.description.sponsorshipComisión Nacional de Ciencia y Tecnología (CONICYT), Chile FONDECYT 1140329 1180157 FONDECYT 3160298 FONDAP 15130011 National Institute of Health HL113167 HL095070 CONICYTes_ES
Publisherdc.publisherPublic library sciencees_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.uri*
Sourcedc.sourcePlos onees_ES
Títulodc.titleAutophagy mediates tumor necrosis factor-alpha-induced phenotype switching in vascular smooth muscle A7r5 cell linees_ES
Document typedc.typeArtículo de revistaes_ES
Indexationuchile.indexArtículo de publicación ISIes_ES

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