Extracellular vesicles derived from fat-laden hepatocytes undergoing chemical hypoxia promote a pro-fibrotic phenotype in hepatic stellate cells

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dc.contributor.authorHernandez, Alejandra
dc.contributor.authorReyes, Daniela
dc.contributor.authorGeng, Yana
dc.contributor.authorPablo Arab, Juan
dc.contributor.authorCabrera, Daniel
dc.contributor.authorSepulveda, Rolando
dc.contributor.authorSolis, Nancy
dc.contributor.authorBuist-Homan, Manon
dc.contributor.authorArrese, Marco
dc.contributor.authorMoshage, Han
dc.date.accessioned2025-01-23T19:49:08Z
dc.date.available2025-01-23T19:49:08Z
dc.date.issued2020
dc.description.abstractBackground: The transition from steatosis to non-alcoholic steatohepatitis (NASH) is a key issue in non-alcoholic fatty liver disease (NAFLD). Observations in patients with obstructive sleep apnea syndrome (OSAS) suggest that hypoxia contributes to progression to NASH and liver fibrosis, and the release of extracellular vesicles (EVs) by injured hepatocytes has been implicated in NAFLD progression.
dc.description.abstractAim: To evaluate the effects of hypoxia on hepatic pro-fibrotic response and EV release in experimental NAFLD and to assess cellular crosstalk between hepatocytes and human hepatic stellate cells (LX-2).
dc.description.abstractMethods: HepG2 cells were treated with fatty acids and subjected to chemically induced hypoxia using the hypoxia-inducible factor 1 alpha (HIF-1 alpha) stabilizer cobalt chloride (CoCl2). Lipid droplets, oxidative stress, apoptosis and pro-inflammatory and pro-fibrotic-associated genes were assessed. EVs were isolated by ultracentrifugation. LX-2 cells were treated with EVs from hepatocytes. The CDAA-fed mouse model was used to assess the effects of intermittent hypoxia (IH) in experimental NASH.
dc.description.abstractResults: Chemical hypoxia increased steatosis, oxidative stress, apoptosis and pro-inflammatory and pro-fibrotic gene expressions in fat-laden HepG2 cells. Chemical hypoxia also increased the release of EVs from HepG2 cells. Treatment of LX2 cells with EVs from fat-laden HepG2 cells undergoing chemical hypoxia increased expression pro-fibrotic markers. CDAA-fed animals exposed to IH exhibited increased portal inflammation and fibrosis that correlated with an increase in circulating EVs.
dc.description.abstractConclusion: Chemical hypoxia promotes hepatocellular damage and pro-inflammatory and pro-fibrotic signaling in steatotic hepatocytes both in vitro and in vivo. EVs from fat-laden hepatocytes undergoing chemical hypoxia evoke pro-fibrotic responses in LX-2 cells.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.bbadis.2020.165857
dc.identifier.eissn1879-260X
dc.identifier.issn0925-4439
dc.identifier.urihttps://doi.org/10.1016/j.bbadis.2020.165857
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100483
dc.identifier.wosidWOS:000559983700018
dc.issue.numero10
dc.language.isoen
dc.revistaBiochimica et biophysica acta-molecular basis of disease
dc.rightsacceso restringido
dc.subjectNonalcoholic fatty liver disease
dc.subjectLiver fibrosis
dc.subjectHypoxia
dc.subjectExtracellular vesicles
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleExtracellular vesicles derived from fat-laden hepatocytes undergoing chemical hypoxia promote a pro-fibrotic phenotype in hepatic stellate cells
dc.typeartículo
dc.volumen1866
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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