Effect of fibroblast growth factor 21 on hepatic fibrosis in mice and its mechanism

Objective To investigate the effect of fibroblast growth factor 21 (FGF21) on hepatic fibrosis in mice and the mechanism of its action. Methods Male ICR mice were randomly divided three groups: control group, model group (treated with CCl4) , and treatment group (treated with CCl4+ 1. 0 mg/kg FGF21) . All mice were sacrificed to collect serum and liver tissues after 36 consecutive days of treatment. Serum levels of alanine transaminase (ALT) , aspartate aminotransferase (AST) , alkaline phosphatase (ALP) , total bilirubin (TBil) , interleukin-6 (IL-6) , interleukin-1β (IL-1β) , and tumor necrosis factor-α (TNF-α) were measured. Liver pathological changes were analyzed by Masson staining. The hepatic 4-hydroxyproline (4-Hyp) level was measured using a hydroxyproline detection kit. The mRNA levels of hepatic collagen I, α-smooth muscle actin (α-SMA) , transforming growth factor-β (TGF-β) , IL-6, IL-1β, and TNF-α were determined by quantitative real-time PCR. Comparison between multiple groups was made by one-way analysis of variance, and comparison between any two groups weas made using the LSD-t test. Results The Masson staining showed that the model group had a significantly higher degree of hepatic fibrosis than the control group, and the treatment group had a significantly lower degree of hepatic fibrosis than the model group. The model group had significantly higher serum levels of ALT, AST, ALP, and TBil (all P < 0. 05) , and the treatment group showed significant reductions in the above parameters compared with the model group (all P < 0. 05) . Enzyme-linked immunosorbent assay indicated that the model group had significantly higher serum levels of IL-1β, IL-6, and TNF-α than the control group (all P < 0. 05) , and the treatment group showed significant reductions in the above parameters compared with the model group (all P < 0. 05) . The hepatic 4-Hyp level and mRNA levels of collagen I and α-SMA were significantly higher in the model group than in the control group (P = 0. 04, < 0. 001, and < 0. 001) , and they were significantly lower in the treatment group than in the model group (P = 0. 005, < 0. 001, and < 0. 001) . The hepatic mRNA levels of TGF-β, IL-6, IL-1β, and TNF-α were significantly higher in the model group than in the control group (all P < 0. 001) , and they were significantly lower in the treatment group than in the control group (all P < 0. 001) . Conclusion FGF21 attenuates hepatic fibrogenesis in mice, possibly by inhibiting the expression of TGF-β, IL-6, IL-1β, and TNF-α in the liver.