Kai Liu1, Ming-Gao Guo1, Xiao-Li Lou1, Xiao-Ya Li1, Yang Xu1, Wei-Dan Ji1, Xuan-Dong Huang1, Jia-He Yang1, Ji-Cheng Duan1. 1. 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.
Abstract
AIM: 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. CONCLUSION: 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.
AIM: 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. CONCLUSION: 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: Liu Yang; Youngmi Jung; Alessia Omenetti; Rafal P Witek; Steve Choi; Hendrika M Vandongen; Jiawen Huang; Gianfranco D Alpini; Anna Mae Diehl Journal: Stem Cells Date: 2008-05-29 Impact factor: 6.277
Authors: Vladimir V Kalinichenko; Dibyendu Bhattacharyya; Yan Zhou; Galina A Gusarova; Wooram Kim; Brian Shin; Robert H Costa Journal: Hepatology Date: 2003-01 Impact factor: 17.425
Authors: Fereshteh Parviz; Christine Matullo; Wendy D Garrison; Laura Savatski; John W Adamson; Gang Ning; Klaus H Kaestner; Jennifer M Rossi; Kenneth S Zaret; Stephen A Duncan Journal: Nat Genet Date: 2003-07 Impact factor: 38.330