Enhanced effect of soluble transforming growth factor-β receptor II and IFN-γ fusion protein in reversing hepatic fibrosis

OBJECTIVE: To examine the in vivo anti-fibrotic effect of rat soluble transforming growth factor β receptor II (RsTβRII) and IFN-γ fusion protein (RsTβRII-IFN-γ) in rat hepatic fibrosis model. METHODS: Model rats were divided into five groups and treated i.m. for 8 weeks: 1) fibrotic model group (each rat, 100 μl of 0.9% NaCl day(-1)); 2) RsTβRII-IFN-γ treatment group (each rat, 0.136 mg· day(-1)); 3) IFN-γ treatment group (each rat, 7.5 MU· day(-1)); 4) RsTβRII treatment group (each rat, 0.048 mg· day(-1)); and 5) mixture of IFN-γ and RsTβRII treatment group (each rat, IFN-γ 7.5 MU· day(-1)+ RsTβRII 0.048 mg· day(-1)). After treatment, hepatic fibrogenesis was evaluated by histopathological analysis and measurement of collagen III, α-smooth muscle actin (α-SMA), TGF-β1, TGF-βRII and their mRNA. RESULTS: Immunohistochemistry, Western blot and real-time RT-PCR showed that RsTβRII-IFN-γ treatment significantly inhibited liver expression of collagen III, α-SMA, TGF-β1 and TGF-βRII at both protein and mRNA levels. Histopathological analysis also showed that the enhanced anti-fibrotic effects were achieved in model rats treated with RsTβRII-IFN-γ. CONCLUSION: Our results confirmed that RsTβRII-IFN-γ has the enhanced effects in reversing hepatic fibrosis.