title: Hepatocyte nuclear factor 4α induces a tendency of differentiation and activation of rat hepatic stellate cells.
abstract: OBJECTIVE
  To investigate the effect of hepatocyte nuclear factor 4α (HNF4α) on the differentiation and transformation of hepatic stellate cells (HSCs).
  
  
  METHODS
  By constructing the recombinant adenovirus vector expressing HNF4α and HNF4α shRNA vector, and manipulating HNF4α expression in HSC-T6 cells, we explored the influence of HNF4α and its induction capacity in the differentiation of rat HSCs into hepatocytes.
  
  
  RESULTS
  With increased expression of HNF4α mediated by AdHNF4α, the relative expression of Nanog was downregulated in HSC-T6 cells (98.33 ± 12.33 vs 41.33 ± 5.67, P < 0.001). Consequently, the expression of G-P-6 and PEPCK was upregulated (G-P-6: 14.34 ± 3.33 vs 42.53 ± 5.87, P < 0.01; PEPCK: 10.10 ± 4.67 vs 56.56 ± 5.25, P < 0.001), the expression of AFP and ALB was positive, and the expression of Nanog, Type I collagen, α-SMA, and TIMP-1 was significantly decreased. HNF4α also downregulated vimentin expression and enhanced E-cadherin expression. The ultrastructure of HNF4α-induced cells had more mitochondria and ribosomes compared with the parental cells. After silencing HNF4α expression, EPCK, E-cadherin, AFP, and ALB were downregulated and α-SMA and vimentin were upregulated.
  
  
  CONCLUSIONS
  HNF4α can induce a tendency of differentiation of HSCs into hepatocyte-like cells. These findings may provide an effective way for the treatment of liver diseases.
authors.affiliation: Kai Liu, Xiao-Ya Li, Yang Xu, Wei-Dan Ji, Jia-He Yang, Ji-Cheng Duan, Department of Molecular Oncology and Laparoscopic Surgery, Eastern Hepatobiliary Surgical Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Kai Liu, Xiao-Ya Li, Yang Xu, Wei-Dan Ji, Jia-He Yang, Ji-Cheng Duan, Department of Molecular Oncology and Laparoscopic Surgery, Eastern Hepatobiliary Surgical Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Guo
authors.affiliation: Kai Liu, Xiao-Ya Li, Yang Xu, Wei-Dan Ji, Jia-He Yang, Ji-Cheng Duan, Department of Molecular Oncology and Laparoscopic Surgery, Eastern Hepatobiliary Surgical Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Lou
authors.affiliation: Kai Liu, Xiao-Ya Li, Yang Xu, Wei-Dan Ji, Jia-He Yang, Ji-Cheng Duan, Department of Molecular Oncology and Laparoscopic Surgery, Eastern Hepatobiliary Surgical Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Li
authors.affiliation: Kai Liu, Xiao-Ya Li, Yang Xu, Wei-Dan Ji, Jia-He Yang, Ji-Cheng Duan, Department of Molecular Oncology and Laparoscopic Surgery, Eastern Hepatobiliary Surgical Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Kai Liu, Xiao-Ya Li, Yang Xu, Wei-Dan Ji, Jia-He Yang, Ji-Cheng Duan, Department of Molecular Oncology and Laparoscopic Surgery, Eastern Hepatobiliary Surgical Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.
authors.forename: Wei-Dan
authors.initials: WD
authors.lastname: Ji
authors.affiliation: Kai Liu, Xiao-Ya Li, Yang Xu, Wei-Dan Ji, Jia-He Yang, Ji-Cheng Duan, Department of Molecular Oncology and Laparoscopic Surgery, Eastern Hepatobiliary Surgical Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.
authors.forename: Xuan-Dong
authors.initials: XD
authors.lastname: Huang
authors.affiliation: Kai Liu, Xiao-Ya Li, Yang Xu, Wei-Dan Ji, Jia-He Yang, Ji-Cheng Duan, Department of Molecular Oncology and Laparoscopic Surgery, Eastern Hepatobiliary Surgical Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.
authors.forename: Jia-He
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Kai Liu, Xiao-Ya Li, Yang Xu, Wei-Dan Ji, Jia-He Yang, Ji-Cheng Duan, Department of Molecular Oncology and Laparoscopic Surgery, Eastern Hepatobiliary Surgical Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China.
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Duan
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002460:Cell Line; D054338:Cell Transdifferentiation; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000648:ultrastructure; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008930:Mitochondria, Liver / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012270:Ribosomes / Q000378:metabolism / Q000648:ultrastructure; D015398:Signal Transduction; D014162:Transfection
chemical_list: C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D012333:RNA, Messenger
keywords: Adenovirus vector; Differentiation; Hepatic stellate cells; Hepatocyte nuclear factor 4α; Rat