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dc.contributor.authorAntwi, Milton Boaheng
dc.contributor.authorDumitriu, Gianina
dc.contributor.authorSimón-Santamaria, Jaione
dc.contributor.authorSánchez Romano, Javier
dc.contributor.authorLi, Ruomei
dc.contributor.authorSmedsrød, Bård
dc.contributor.authorVik, Anders
dc.contributor.authorEskild, Winnie
dc.contributor.authorSørensen, Karen Kristine
dc.date.accessioned2023-11-21T09:13:48Z
dc.date.available2023-11-21T09:13:48Z
dc.date.issued2023-11-01
dc.description.abstractLiver sinusoidal endothelial cells (LSECs) are fenestrated endothelial cells with a unique, high endocytic clearance capacity for blood-borne waste macromolecules and colloids. This LSEC scavenger function has been insufficiently characterized in liver disease. The Glmp<sup>gt/gt</sup> mouse lacks expression of a subunit of the MFSD1/GLMP lysosomal membrane protein transporter complex, is born normal, but soon develops chronic, mild hepatocyte injury, leading to slowly progressing periportal liver fibrosis, and splenomegaly. This study examined how LSEC scavenger function and morphology are affected in the Glmp<sup>gt/gt</sup> model. FITC-labelled formaldehyde-treated serum albumin (FITC-FSA), a model ligand for LSEC scavenger receptors was administered intravenously into Glmp<sup>gt/gt</sup> mice, aged 4 months (peak of liver inflammation), 9–10 month, and age-matched Glmpwt/wt mice. Organs were harvested for light and electron microscopy, quantitative image analysis of ligand uptake, collagen accumulation, LSEC ultrastructure, and endocytosis receptor expression (also examined by qPCR and western blot). In both age groups, the Glmp<sup>gt/gt</sup> mice showed multifocal liver injury and fibrosis. The uptake of FITC-FSA in LSECs was significantly reduced in Glmp<sup>gt/gt</sup> compared to wild-type mice. Expression of LSEC receptors stabilin-1 (Stab1), and mannose receptor (Mcr1) was almost similar in liver of Glmp<sup>gt/gt</sup> mice and agematched controls. At the same time, immunostaining revealed differences in the stabilin-1 expression pattern in sinusoids and accumulation of stabilin-1-positive macrophages in Glmp<sup>gt/gt</sup> liver. FcγRIIb (Fcgr2b), which mediates LSEC endocytosis of soluble immune complexes was widely and significantly downregulated in Glmp<sup>gt/gt</sup> liver. Despite increased collagen in space of Disse, LSECs of Glmp<sup>gt/gt</sup> mice showed well-preserved fenestrae organized in sieve plates but the frequency of holes >400 nm in diameter was increased, especially in areas with hepatocyte damage. In both genotypes, FITC-FSA also distributed to endothelial cells of spleen and bone marrow sinusoids, suggesting that these locations may function as possible compensatory sites of clearance of blood-borne scavenger receptor ligands in liver fibrosis.en_US
dc.identifier.citationAntwi, Dumitriu, Simón-Santamaria, Sánchez Romano, Li, Smedsrød, Vik, Eskild, Sørensen. Liver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIB, yet maintain a preserved fenestration the Glmp<sup> gt/gt</sup> mouse model of slowly progressing liver fibrosis. PLOS ONE. 2023en_US
dc.identifier.cristinIDFRIDAID 2199043
dc.identifier.doi10.1371/journal.pone.0293526
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/31827
dc.language.isoengen_US
dc.publisherPLOSen_US
dc.relation.journalPLOS ONE
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleLiver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIB, yet maintain a preserved fenestration the Glmp gt/gt mouse model of slowly progressing liver fibrosisen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)