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Title: Galectin-3 ablation enhances liver steatosis, but attenuates inflammation and IL-33-dependent fibrosis in obesogenic mouse model of nonalcoholic steatohepatitis
Authors: Jeftic, Ilija
Jovicic, Nemanja
Pantic, Jelena
Arsenijevic, Nebojsa
Lukic, Miodrag
Pejnović, Nada
Issue Date: 2015
Abstract: © 2015 Uninversity of Michigan. All rights reserved. The importance of Galectin-3 (Gal-3) in obesity-associated liver pathology is incompletely defined. To dissect the role of Gal-3 in fibrotic nonalcoholic steatohepatitis (NASH), Gal-3-deficient (LGALS3–/–) and wild-type (LGALS3+/+) C57Bl/6 mice were placed on an obesogenic high fat diet (HFD, 60% kcal fat) or standard chow diet for 12 and 24 wks. Compared to WT mice, HFD-fed LGALS3–/– mice developed, in addition to increased visceral adiposity and diabetes, marked liver steatosis, which was accompanied with higher expression of hepatic PPAR-γ, Cd36, Abca-1and FAS. However, as opposed to LGALS3–/– mice, hepatocellular damage, inflammation and fibrosis were more extensive in WT mice which had an elevated number of mature myeloid dendritic cells, proinflammatory CD11b+Ly6Chi monocytes/macrophages in liver, peripheral blood and bone marrow, and increased hepatic CCL2, F4/80, CD11c, TLR4, CD14, NLRP3 inflammasome, IL-1βand NADPH-oxidase enzymes mRNA expression. Thus, obesitydriven greater steatosis was uncoupled with attenuated fibrotic NASH in Gal-3-deficient mice. HFD-fed WT mice had a higher number of hepatocytes that strongly expressed IL-33 and hepatic CD11b+IL-13+ cells, increased levels of IL-33 and IL-13 and upregulated IL-33, ST2and IL-13 mRNA in liver compared with LGALS3–/– mice. IL-33 failed to induce ST2 upregulation and IL-13 production by LGALS3–/– peritoneal macrophages in vitro. Administration of IL-33 in vivoenhanced liver fibrosis in HFD-fed mice in both genotypes, albeit to a significantly lower extent in LGALS3–/– mice, which was associated with less numerous hepatic IL-13-expressing CD11b+ cells. The present study provides evidence of a novel role for Gal-3 in regulating IL-33-dependent liver fibrosis.
Type: article
DOI: 10.2119/molmed.2014.00178
ISSN: 1076-1551
SCOPUS: 2-s2.0-84940781164
Appears in Collections:Faculty of Medical Sciences, Kragujevac

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