论文部分内容阅读
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 HNF4αshRNA 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 HNF4αmediated 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 treatmentof 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 vectors, 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 HNF4αmediated 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). The expression of GP-6 and PEPCK was upregulated (GP-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 HNF 4α-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.