Enhanced effect of soluble transforming growth factor-beta receptor II and IFN-gamma fusion protein in reversing hepatic fibrosis.
OBJECTIVE
To examine the in vivo anti-fibrotic effect of rat soluble transforming growth factor beta receptor II (RsTbetaRII) and IFN-gamma fusion protein (RsTbRII-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 microl of 0.9% NaCl day superset-1); 2) RsTbetaRII-IFN-gamma treatment group (each rat, 0.136 mg x day(-1); 3) IFN-gamma treatment group (each rat, 7.5 MU x day(-1); 4) RsTbetaRII treatment group (each rat, 0.048 mg x day(-1); and 5) mixture of IFN-gamma and RsTbetaRII treatment group (each rat, IFN-gamma 7.5 MU x day(-1)+ RsTbetaRII 0.048 mg x day(-1). After treatment, hepatic fibrogenesis was evaluated by histopathological analysis and measurement of collagen III, alpha-smooth muscle actin (alpha-SMA), TGF-beta1, TGF-betaRII and their mRNA.


RESULTS
Immunohistochemistry, Western blot and real-time RT-PCR showed that RsTbetaRII-IFN-gamma treatment significantly inhibited liver expression of collagen III, alpha-SMA, TGF-beta1 and TGF-betaRII at both protein and mRNA levels. Histopathological analysis also showed that the enhanced anti-fibrotic effects were achieved in model rats treated with RsTbetaRII-IFN-gamma.


CONCLUSIONS
Our results confirmed that RsTbetaRII-IFN-gamma has the enhanced effects in reversing hepatic fibrosis.
Yao
H
H
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, China.
Pan
J
J
Qian
Y
Y
Pei
Z
Z
Bader
A
A
Brockmeyer
N H
NH
Altmeyer
P
P
Zhang
Lihuang
L
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D017931:DNA Primers; D004195:Disease Models, Animal; D005784:Gene Amplification; D007371:Interferon-gamma / Q000235:genetics / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*
D017931:DNA Primers; D018125:Receptors, Transforming Growth Factor beta; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma; D002251:Carbon Tetrachloride; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II