Kim Kyung-Hyun, Kim Hyun-Chul, Hwang Mee-Yul, Oh Hoon-Kyu, Lee Tae-Sung, Chang Young-Chae, Song Ho-Jung, Won Nam-Hee, Park Kwan-Kyu
Department of Pathology, Catholic University of Daegu, College of Medicine, 3056-6 Daemyung 4-Dong, Nam-Gu, Daegu 705-718, Republic of Korea.
Biochem Biophys Res Commun. 2006 May 19;343(4):1072-8. doi: 10.1016/j.bbrc.2006.03.087. Epub 2006 Mar 23.
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.
肝纤维化是由慢性肝炎、酒精和有毒物质对肝脏造成的慢性损伤所致。肝纤维化的一个特征是细胞外基质（ECM）蛋白的积累，其通过形成纤维瘢痕扭曲肝结构，而随后再生结节的形成则定义为肝硬化。转化生长因子（TGF）-β1是最强大的促纤维化介质之一，在肝硬化的发展过程中起主要作用，并调节ECM基因表达和基质降解。本研究通过RNA干扰阐明肝纤维化形成过程中TGF-β1介导信号的变化。在本实验中，与对照组相比，TGF-β1小干扰RNA（siRNAs）降低了四氯化碳注射小鼠肝脏中TGF-β1的表达，同时I型胶原蛋白和α-平滑肌肌动蛋白的表达也降低。总之，本研究表明TGF-β1 siRNAs在肝硬化小鼠模型中抑制TGF-β1表达，可能是预防人类肝硬化的一种良好治疗策略。
