Hepatic stellate cells induce an inflammatory phenotype in Kupffer cells via the release of extracellular vesicles

Simple item page
dc.contributor.authorGeng, Yana
dc.contributor.authorWang, Junyu
dc.contributor.authorSerna-Salas, Sandra Alejandra
dc.contributor.authorVillanueva, Alejandra Hernandez
dc.contributor.authorBuist-Homan, Manon
dc.contributor.authorArrese, Marco
dc.contributor.authorOlinga, Peter
dc.contributor.authorBlokzijl, Hans
dc.contributor.authorMoshage, Han
dc.date.accessioned2025-01-20T20:08:09Z
dc.date.available2025-01-20T20:08:09Z
dc.date.issued2023
dc.description.abstractLiver fibrosis is the response of the liver to chronic liver inflammation. The communication between the resident liver macrophages (Kupffer cells [KCs]) and hepatic stellate cells (HSCs) has been mainly viewed as one-directional: from KCs to HSCs with KCs promoting fibrogenesis. However, recent studies indicated that HSCs may function as a hub of intercellular communications. Therefore, the aim of the present study was to investigate the role of HSCs on the inflammatory phenotype of KCs. Primary rat HSCs and KCs were isolated from male Wistar rats. HSCs-derived conditioned medium (CM) was harvested from different time intervals (Day 0-2: CM-D2 and Day 5-7: CM-D7) during the activation of HSCs. Extracellular vesicles (EVs) were isolated from CM by ultracentrifugation and evaluated by nanoparticle tracking analysis and western blot analysis. M1 and M2 markers of inflammation were measured by quantitative PCR and macrophage function by assessing phagocytic capacity. CM-D2 significantly induced the inflammatory phenotype in KCs, but not CM-D7. Neither CM-D2 nor CM-D7 affected the phagocytosis of KCs. Importantly, the proinflammatory effect of HSCs-derived CM is mediated via EVs released from HSCs since EVs isolated from CM mimicked the effect of CM, whereas EV-depleted CM lost its ability to induce a proinflammatory phenotype in KCs. In addition, when the activation of HSCs was inhibited, HSCs produced less EVs. Furthermore, the proinflammatory effects of CM and EVs are related to activating Toll-like receptor 4 (TLR4) in KCs. In conclusion, HSCs at an early stage of activation induce a proinflammatory phenotype in KCs via the release of EVs. This effect is absent in CM derived from HSCs at a later stage of activation and is dependent on the activation of TLR4 signaling pathway.
dc.description.funderChina Scholarship Council
dc.fuente.origenWOS
dc.identifier.doi10.1002/jcp.31086
dc.identifier.eissn1097-4652
dc.identifier.issn0021-9541
dc.identifier.urihttps://doi.org/10.1002/jcp.31086
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/91874
dc.identifier.wosidWOS:001043670000001
dc.issue.numero10
dc.language.isoen
dc.pagina.final2303
dc.pagina.inicio2293
dc.revistaJournal of cellular physiology
dc.rightsacceso restringido
dc.subjectextracellular vesicles
dc.subjecthepatic stellate cells
dc.subjectinflammation
dc.subjectKupffer cells
dc.subjecttoll-like receptor 4
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleHepatic stellate cells induce an inflammatory phenotype in Kupffer cells via the release of extracellular vesicles
dc.typeartículo
dc.volumen238
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas