Digestive diseases and sciences · 2016
Knockdown of Astrocyte Elevated Gene-1 Inhibits Activation of Hepatic Stellate Cells.
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Chen Lei, Guo Yong-Ze, Li Ai-di, Ma Jun-Ji, Hao Hui-Yao, Zhang Di, Wang Yan, Ji Chen-Guang, Qi Wei, Wang Jia, Jiang Hui-Qing
Аннотация
BACKGROUND: Astrocyte elevated gene-1 (AEG-1) is a positive regulator of tumorigenesis and a valuable prognostic marker of a diverse array of cancers, including liver cancer; however, the relationship between AEG-1 and hepatic fibrogenesis is not known.
OBJECTIVE: The objective of this study was to explore the expression of AEG-1 during hepatic fibrogenesis and determine how AEG-1 regulates the profibrogenic phenotype of hepatic stellate cells (HSCs).
METHODS: The levels of AEG-1 were monitored in the fibrotic livers and transforming growth factor-β (TGF-β)- or lipopolysaccharide (LPS)-stimulated HSCs. The expression of AEG-1 was knocked down by lentivirus-mediated short hairpin RNA in HSCs, and collagen expression, proliferation assays, apoptosis induction studies, and migration assays were simultaneously conducted in vitro.
RESULTS: AEG-1 expression was increased in the fibrotic livers. At the cellular level, TGF-β or LPS stimulation, which caused HSC activation, induced AEG-1 expression in HSC-T6 and primary rat HSCs (P < 0.05). Knockdown of AEG-1 inhibited collagen I and α-smooth muscle actin expression (P < 0.05), reduced cell proliferation (P < 0.05) and motility (P < 0.05), and induced cell apoptosis (P < 0.05) in HSCs. This antifibrotic effect caused by lack of AEG-1 was associated with the inactivation of PI3K/Akt and the mitogen-activated protein kinase pathway.
CONCLUSIONS: Knockdown of AEG-1 suppressed the activation of HSCs by modulating the phenotype and inducing apoptosis. AEG-1 might be a potential target in treatment of hepatic fibrosis.
OBJECTIVE: The objective of this study was to explore the expression of AEG-1 during hepatic fibrogenesis and determine how AEG-1 regulates the profibrogenic phenotype of hepatic stellate cells (HSCs).
METHODS: The levels of AEG-1 were monitored in the fibrotic livers and transforming growth factor-β (TGF-β)- or lipopolysaccharide (LPS)-stimulated HSCs. The expression of AEG-1 was knocked down by lentivirus-mediated short hairpin RNA in HSCs, and collagen expression, proliferation assays, apoptosis induction studies, and migration assays were simultaneously conducted in vitro.
RESULTS: AEG-1 expression was increased in the fibrotic livers. At the cellular level, TGF-β or LPS stimulation, which caused HSC activation, induced AEG-1 expression in HSC-T6 and primary rat HSCs (P < 0.05). Knockdown of AEG-1 inhibited collagen I and α-smooth muscle actin expression (P < 0.05), reduced cell proliferation (P < 0.05) and motility (P < 0.05), and induced cell apoptosis (P < 0.05) in HSCs. This antifibrotic effect caused by lack of AEG-1 was associated with the inactivation of PI3K/Akt and the mitogen-activated protein kinase pathway.
CONCLUSIONS: Knockdown of AEG-1 suppressed the activation of HSCs by modulating the phenotype and inducing apoptosis. AEG-1 might be a potential target in treatment of hepatic fibrosis.