Changes in cytokines and signaling pathways in different stages of hepatic fibrosis in rats

Background & Purpose: Liver fibrosis is a disease that seriously threatens people’s health, and its etiopathogenesis has not been described clearly. Experimental Approach: Female rats were subjected to common bile duct ligation (BDL) for one month, and male rats were treated with thioacetamide for 23 weeks. The expression of cytokines, signal pathways, histopathology in liver and biochemical indexes in serum were detected. Key Results: The levels of transaminases in serum and hydroxyproline and α-smooth muscle actin in the liver were remarkably increased in both models, although the degree of liver fibrosis was more severe in thioacetamide rats than in BDL rats. However, the levels of IL-1α, IL-4, IL-10, TNFα, MCP-1, PDGF-BB, p-Akt and p-STAT5 decreased, and the levels of IL-18, TGFβ1 and p-p70s6k increased in the livers of BDL rats, while the levels of IL-1α, IL-4, IL-10, IL-1β, IL-6 and IL-12p70, TNFα, MCP-1, PDGF-BB, p-CREB, p-JNK, p-NFκB, p-Akt, p-p70s6k, p-STAT3 and p-STAT5 decreased, and the levels of IL-18 and TGF-β1 increased in the livers in thioacetamide rats. Conclusion and Implications: These data suggest that TGFβ1 and IL-18 may be the main fibrogenic factors at different stages of liver fibrosis and that the levels of inflammation-associated cytokines and signaling pathway components decrease as the severity of hepatic fibrosis progresses. Therefore, it may be better to apply anti-inflammatory drugs in the early stage or use these drugs which facilitating more inflammatory cells or cytokines into liver tissue at the end stage of hepatic fibrosis.