Hepatocyte nuclear factor 4α induces a tendency of differentiation and activation of rat hepatic stellate cells

AIM: To investigate the effect of hepatocyte nuclear factor 4 alpha (HNF4 alpha) on the differentiation and transformation of hepatic stellate cells (HSCs). METHODS: By constructing the recombinant adenovirus vector expressing HNF4 alpha and HNF4 alpha shRNA vector, and manipulating HNF4 alpha expression in HSC-T6 cells, we explored the influence of HNF4 alpha and its induction capacity in the differentiation of rat HSCs into hepatocytes. RESULTS: With increased expression of HNF4 alpha mediated by AdHNF4 alpha, 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. collagen, alpha-SMA, and TIMP-1 was significantly decreased. HNF4 alpha also downregulated vimentin expression and enhanced E-cadherin expression. The ultrastructure of HNF4 alpha-induced cells had more mitochondria and ribosomes compared with the parental cells. After silencing HNF4 alpha expression, EPCK, E-cadherin, AFP, and ALB were downregulated and alpha-SMA and vimentin were upregulated. CONCLUSION: HNF4 alpha 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.