ZEB1 regulates the activation of hepatic stellate cells through Wnt/beta-catenin signaling pathway

摘要

Zinc finger E-box binding homeobox 1 (ZEB1) (previously known as TCF8), a transcriptional repressor, is a member of the zinc-finger family of proteins. Numerous studies have demonstrated that abnormal expression of ZEB1 in many types of liver disease including hepatocellular carcinoma (HCC). Liver fibrosis is the basis and central link in the progression of liver disease. Thereby, the function of ZEB1 in liver fibrosis has been investigated. The aim of the present study was to investigate the role of ZEB1 in liver fibrosis and to elucidate the mechanism. In this study, we explored the effect of ZEB1 in hepatic stellate cells (HSCs) activation and the regulatory mechanism of the Wnt/beta-catenin signaling pathway. Additionally, ZEB1 positively regulated the expression levels of alpha-SMA and Col.I in vivo and in vitro, which were correlated with the activated HSCs. Furthermore, overexpression of ZEB1 could inhibit HSCs apoptosis and promote IL-6 and TNF-alpha secretion in LX-2 cells. Conversely, ZEB1 silencing led to the promotion of cell proliferation and the reduction of IL-6 and TNF-alpha secretion in LX-2 cells. Mechanically, canonical Wnt/beta-catenin signaling pathway could be regulated by ZEB1. Collectively, the data suggested that ZEB1 might play a significant role in the activation of LX-2 cells, and Wnt/beta-catenin signaling pathway might participate in this progression.