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

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

SUBMITTER: Liu K 

PROVIDER: S-EPMC4438019 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature