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 beta receptor II (RsT beta RII) and IFN-gamma fusion protein (RsT beta RII-IFN-gamma) 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 mu l of 0.9% NaCl day(-1)); 2) RsT beta RII-IFN-gamma treatment group (each rat, 0.136 mg.day(-1)); 3) IFN-gamma treatment group (each rat, 7.5 MU.day(-1)); 4) RsT beta RII treatment group (each rat, 0.048mg.day(-1)); and 5) mixture of IFN-gamma and RsT beta RII treatment group (each rat, IFN-gamma 7.5 MU.day(-1)+ RsT beta RII 0.048 mg.day(-1)). After treatment, hepatic fibrogenesis was evaluated by histopathological analysis and measurement of collagen III, alpha-smooth muscle actin (alpha-SMA), TGF-beta 1, TGF-beta RII and their mRNA. Results: Immunohistochemistry, Western blot and real-time RT-PCR showed that RsT beta RII-IFN-gamma treatment significantly inhibited liver expression of collagen III, alpha-SMA, TGF-beta 1 and TGF-beta RII at both protein and mRNA levels. Histopathological analysis also showed that the enhanced anti-fibrotic effects were achieved in model rats treated with RsT beta RII-IFN-gamma. Conclusion: Our results confirmed that RsT beta RII-IFN-gamma has the enhanced effects in reversing hepatic fibrosis.