Regulation of Macrophage Activation During Hepatic Fibrogenic Response By Socs1 in Hepatic Stellate Cells

Background and Aim: Hepatic stellate cells (HSC) are the main precursors of myofibroblasts, key mediators liver fibrosis (LF). Activation HSCs their differentiation towards myofibroblasts is driven by cytokines growth factors secreted liver-resident macrophages recruited monocytes. Conversely, produced can influence macrophage functions. SOCS1 a regulator several implicated in fibrosis. To investigate role during fibrosis, we generated mice lacking HSC (Socs1HSC). Methods: Socs1HSC Socs1fl/fl were treated with carbon tetrachloride (CCl4) or fed choline-deficient, L-amino acid-defined, high-fat diet (CDA-HFD). Following exposure to CCl4 CDA-HFD, showed increased LF compared control that was associated activation HSC, collagen deposition loss hepatic lobular architecture. Results: Livers significant increase expression genes coding for smooth muscle actin, collagens, matrix metalloproteases (MMP), chemokines, factors. SOCS1-deficient heightened basal elevated modulate immune cell recruitment The livers displayed mononuclear infiltration proinflammatory phenotype (CD11b+Ly6G-Ly6ChiCCR2+). Importantly, this monocyte population contained CCR2hiCX3CR1+ transitional state monocyte-derived macrophages, suggesting impaired transition resolution type macrophages. Conclusion: Our findings indicate crucial fibrogenic response. exerts its anti-fibrotic functions modulating ECM remodeling enzymes as well chemokines promote recruitment, resolution.