Regulation of high-fat diet-induced liver fibrosis by SOCS1 expression in hepatic stellate cells

BackgroundHepatic stellate cells (HSC) are the key mediators of fibrosis development in non-alcoholic fatty liver disease (NAFLD). Hepatic inflammation induced by high-fat diet activates HSCs, which differentiate to myofibroblasts and produce extracellular fibrillar matrix. HSC activation during hepatic fibrogenesis is modulated cytokines growth factors produced stressed hepatocytes macrophages. SOCS1 a negative feedback regulator certain implicated fibrosis.AimThe goal this study was understand regulatory functions HSCs NAFLD-induced fibrosis.MethodologyMice lacking specifically (Socs1ΔHSC) control Socs1-floxed (Socs1fl/fl) mice were fed choline-deficient L-amino acid-defined (CDA-HFD) or normal for 14 weeks. Body weight gain regularly monitored. Serum alanine aminotransferase levels assessed at endpoint. Fibrosis evaluated Sirius red staining hydroxyproline content, myofibroblast differentiation immunohistochemistry. Expression genes encoding pro-fibrogenic factors, cytokines, chemokines, phenotype numbers intrahepatic leukocytes evaluated.ResultsSocs1ΔHSC showed increased liver/body ratio displayed collagen deposition differentiation. Induction Acta2, Col1a1, Pdgfb, IL1b Ccl2 significantly elevated Socs1ΔHSC compared Socs1fl/fl controls CDA-HFD. Tgfb gene induction comparable between two groups, however, livers SMAD3 phosphorylation. The fibrotic inflammatory cell infiltration, flow cytometry analysis revealed myeloid cells, granulocytes myeloid-derived dendritic cells. harbored Ly6ChiCCR2+ pro-inflammatory macrophages, largely comprised Ly6ChiCCR2+CX3CR1+ suggesting impaired transition anti-inflammatory macrophages.ConclusionOur findings show that exerts non-redundant critical attenuating diet-induced response development.