Bi Wan-Rong, Yang Chang-Qing, Shi Qing
Department of Gastroenterology and Digestive Disease Institute, Tongji Hospital Branch, Tongji University, Shanghai, China.
Hepatogastroenterology. 2012 Sep;59(118):1960-3. doi: 10.5754/hge11750.
The epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are crucial for the regulation of cellular plasticity during liver fibrosis. Transforming growth factor (TGF)-β1 is an important cytokine for the induction of the EMT in liver fibrosis. TGF-β1 signaling induces the EMT through various signaling mechanisms and is the predominant agent mediating these fibrotic changes. Chronic exposure to TGF-β1 induces the transition of hepatocytes to collagen-producing mesenchymal cells, prolonged exposure of hepatocytes to TGF-β1 increases the expression of collagen and induces cytoskeletal rearrangement that resembles the EMT. These morphological and molecular alterations may provide the foundation for liver fibrosis. This review discussed the relation and mechanisms between EMT and liver fibrosis and ulteriorly elaborated on TGF-β1 induced EMT and each of their roles in liver fibrosis. Better understanding of the cellular and molecular characteristics of the cirrhotic hepatocyte may enable the development of chemo-preventative agents for liver fibrosis.
上皮-间质转化(EMT)和间质-上皮转化(MET)对于肝纤维化过程中细胞可塑性的调节至关重要。转化生长因子(TGF)-β1是肝纤维化中诱导EMT的重要细胞因子。TGF-β1信号通过多种信号机制诱导EMT,是介导这些纤维化变化的主要因子。长期暴露于TGF-β1会诱导肝细胞向产生胶原蛋白的间充质细胞转变,肝细胞长期暴露于TGF-β1会增加胶原蛋白的表达并诱导类似于EMT的细胞骨架重排。这些形态和分子改变可能为肝纤维化奠定基础。本综述讨论了EMT与肝纤维化之间的关系和机制,并进一步阐述了TGF-β1诱导的EMT及其在肝纤维化中的各自作用。更好地了解肝硬化肝细胞的细胞和分子特征可能有助于开发肝纤维化的化学预防药物。