TGF-β1/Smad信号通路在肝纤维化中的研究进展

Research Progress of TGF-β1/Smad Signaling Pathways in Liver Fibrosis

肝纤维化是各种慢性肝病发展的终末阶段,严重威胁人类健康,肝移植是根治肝纤维化的有效方法,但其应用受到肝源短缺的限制,因此寻求肝纤维化治疗靶点、突破肝纤维化治疗具有重要意义。肝纤维化的发生过程是一个复杂的级联反应,多种致纤维因子通过相应的信号通路作用于靶细胞,使之产生致纤维化的各种生物学应答,人转化生长因子β1(Transforming Growth Factorβ1,TGF-β1)是其中最重要的致纤维化因子,Smad蛋白(Drosophila Mothers Against Decapentaplegic Protein)家族是TGF-β1信号传至核内关键的下游信号分子,TGF-β1/Smad信号通路在肝纤维化中发挥主要作用,采取不同措施阻断或调控该信号的传导可作为防治肝纤维化的重要策略,是治疗肝硬化的重要靶点,本文在总结TGF-β1/Smad信号通路在肝纤维化过程中的作用机理的基础上,综述了近年来基于此而提出的各项临床治疗策略及其研究进展。

Liver fibrosis is the terminal stage of a variety of chronic liver diseases, it seriously threatens human health. Liver transplantation is an effective method for the cure of liver fibrosis, but its amplification is limited by the shortage of liver source, therefore, there is no satisfactory treatment yet. To find new therapeutic targets, it is important to make a breakthrough of liver fibrosis. Liver fibrosis is a complex cascade process. Various profibrogenic factors act on the target cells via corresponding signal pathway, it causes various biological responses that result in liver fibrosis. TGF-β1 is one of the most important fibrosis factors, Smad proteins play an important role in the process of TGF-β1 causing liver fibrosis, so TGF-β1 / Smad signaling pathways play a major role in liver fibrosis.Therefore, blocking or regulating TGF-β1/Smad signaling transduction pathways can be an important strategy to treat liver fibrosis.TGF-β1/Smad signaling pathways are important therapeutic targets for the treatment of liver cirrhosis, so in this paper, we reviewd the recent research progress of TGF-β1/Smad signaling pathways in liver fibrosis, including summaries of the source of TGF-β1 and TGF-β1/Smad composition, signal transduction, biological effects and new treatment measures based on them.