title: Role of CTGF gene promoter methylation in the development of hepatic fibrosis.
abstract: Connective tissue growth factor (CTGF) plays a critical role in the hepatic stellate cells (HSCs)-mediated development of hepatic fibrosis. Nevertheless, the effects of CTGF gene promoter methylation in the pathogenesis of hepatic fibrosis remain largely unknown. In the current study, we isolated and overexpressed CTGF in primary HSCs. We analyzed the CTGF gene promoter methylation inHSCs that undergo a phenotypic change into myofibroblast-like cellsthat express α-smooth muscle actin (α-SMA) in vitro and in vivo in a CCl4-induced rat hepatic fibrosis model. We found that CTGF promoted the phenotypic changes of HSCs into myofibroblasts in vitro, while inhibition of CTGF promoter methylation augmented the process, suggesting that CTGF gene promoter methylation may negatively regulate hepatic fibrosis. In vivo, CCl4 induced hepatic fibrosis in rats, and the severity of hepatic fibrosis inversely correlated with the levels of CTGF gene promoter methylation in HSCs. Together, our data demonstrate that CTGF gene promoter methylation may prevent the development of hepatic fibrosis, and low level of CTGF gene promoter methylation in HSCs may be a predisposing factor for developing liver fibrotic disease.
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Tong
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, China.
authors.forename: Yilin
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine Shanghai 200092, China.
authors.forename: Jiangao
authors.initials: J
authors.lastname: Fan
keywords: Connective tissue growth factor (CTGF); hepatic fibrosis; hepatic stellate cells (HSCs); myofibroblasts; α-smooth muscle actin (α-SMA)