Article

The antifibrotic effect of TGF-beta1 siRNAs in murine model of liver cirrhosis.

Department of Pathology, Catholic University of Daegu, College of Medicine, 3056-6 Daemyung 4-Dong, Nam-Gu, Daegu 705-718, Republic of Korea.
Biochemical and Biophysical Research Communications (impact factor: 2.48). 06/2006; 343(4):1072-8. DOI:10.1016/j.bbrc.2006.03.087
Source: PubMed

ABSTRACT Liver fibrosis results from chronic damage to the liver by chronic hepatitis, alcohol, and toxic agents. A characteristic of liver fibrosis is an accumulation of extracellular matrix (ECM) protein, which distorts the hepatic architecture by forming a fibrous scar, and the subsequent development of regenerating nodules defines cirrhosis. Transforming growth factor (TGF)-beta1, one of the most powerful profibrogenic mediators, plays a major role in the development of liver cirrhosis and regulates ECM gene expression and matrix degradation. This study elucidates the changes of TGF-beta1-mediated signals during liver fibrogenesis by using RNA interference. In this experiment, the TGF-beta1 siRNAs reduced the expression of TGF-beta1 in the livers of CCl(4) injection compared with those of control group, and the expression of type I collagen and alpha-smooth muscle actin was decreased. In conclusion, this study demonstrates that TGF-beta1 siRNAs inhibit TGF-beta1 expression in the murine model of liver cirrhosis and might be a good therapeutic strategy to prevent liver cirrhosis in human.

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Keywords

alpha-smooth muscle actin
 
chronic damage
 
control group
 
extracellular matrix
 
good therapeutic strategy
 
hepatic architecture
 
liver cirrhosis
 
liver fibrogenesis
 
Liver fibrosis results
 
livers
 
matrix degradation
 
murine model
 
powerful profibrogenic mediators
 
regenerating nodules defines cirrhosis
 
regulates ECM gene expression
 
study elucidates
 
TGF-beta1 expression
 
TGF-beta1 siRNAs
 
TGF-beta1-mediated signals
 
Transforming growth factor