The antifibrotic effect of TGF-β1 siRNAs in murine model of liver cirrhosis
The antifibrotic effect of TGF-β1 siRNAs in murine model of liver cirrhosis
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DOI：
10.1016/j.bbrc.2006.03.087
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发表时间：
2006-05-19
影响因子：
3.1
通讯作者：
Park, KK
中科院分区：
文献类型：
--
作者：
Kim, KH;Kim, HC;Park, KK
肝纤维化是由慢性肝炎、酒精和有毒物质对肝脏的慢性损伤引起的。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而扭曲肝结构，并且随后再生结节的发展定义为肝硬化。转化生长因子（TGF）-β 1是最强的促纤维化介质之一，在肝硬化的发展中起主要作用，并调节ECM基因表达和基质降解。本研究利用RNA干扰技术，阐明了TGF-β 1介导的信号在肝纤维化过程中的变化。与对照组相比，TGF-β 1 siRNA抑制了CCl 4注射组大鼠肝脏TGF-β 1的表达，并抑制了I型胶原和α-平滑肌肌动蛋白的表达。总之，本研究表明TGF-β 1 siRNA抑制TGF-β 1在小鼠肝硬化模型中的表达，并且可能是预防人类肝硬化的良好治疗策略。beta 2006 Elsevier Inc. All rights reserved.
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)-beta 1, 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-beta 1-mediated signals during liver fibrogenesis by using RNA interference. In this experiment, the TGF-beta 1 siRNAs reduced the expression of TGF-beta 1 in the livers of CCl4 injection compared with those of control group, and the expression of type I collagen and a-smooth muscle actin was decreased. In conclusion, this study demonstrates that TGF-beta 1 siRNAs inhibit TGF-beta 1 expression in the murine model of liver cirrhosis and might be a good therapeutic strategy to prevent liver cirrhosis in human. beta 2006 Elsevier Inc. All rights reserved.