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

Abstract

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, 100μl 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, 0.048mg · 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. © I. Holzapfel Publishers 2010.