title: Knockdown of Astrocyte Elevated Gene-1 Inhibits Activation of Hepatic Stellate Cells.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
authors.forename: Yong-Ze
authors.initials: YZ
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
authors.forename: Ai-di
authors.initials: AD
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
authors.forename: Jun-Ji
authors.initials: JJ
authors.lastname: Ma
authors.affiliation: Department of Endocrinology and Metabolism, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
authors.forename: Hui-Yao
authors.initials: HY
authors.lastname: Hao
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
authors.forename: Chen-Guang
authors.initials: CG
authors.lastname: Ji
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Qi
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China. jianghq@aliyun.com.
authors.forename: Hui-Qing
authors.initials: HQ
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001652:Bile Ducts / Q000601:surgery; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D004128:Dimethylnitrosamine / Q000633:toxicity; D005786:Gene Expression Regulation / Q000502:physiology; D055785:Gene Knockdown Techniques; D055166:Hepatic Stellate Cells / Q000502:physiology*; D006801:Humans; D008026:Ligation; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000209:etiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D004128:Dimethylnitrosamine
keywords: Activation; Astrocyte elevated gene-1; Hepatic stellate cell; Liver fibrosis