Naiki Takafumi, Nagaki Masahito, Asano Takahiko, Kimata Takayuki, Moriwaki Hisataka
Department of Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Biochem Biophys Res Commun. 2005 Sep 23;335(2):496-500. doi: 10.1016/j.bbrc.2005.07.102.
Hepatocyte nuclear factor 4alpha (HNF-4alpha) is a transcription factor that controls embryonal liver development and that maintains and regulates gene expression in adult liver cells. We have previously demonstrated that transient overexpression of HNF-4alpha up-regulates a number of liver-specific genes in hepatoma cell lines. In this study, we extend these studies by assessing the functional role of HNF-4alpha in regulating cellular viability and liver-specific functions of primary rat hepatocytes. In cells transfected with an adenovirus vector carrying rat HNF-4alpha cDNA, induction and maintenance of liver-specific genes and functions were observed over a long-term culture, which might be associated with the prevention of a rapid loss of the mitochondrial membrane potential. In addition, we demonstrated that transthyretin mRNA was up-regulated by HNF-4alpha in primary hepatocytes, but not in hepatoma cells. These results indicate that HNF-4alpha plays a role in the maintenance of morphologically and biochemically functional hepatocytes and that the difference in expression of liver-specific genes induced by HNF-4alpha may depend on a differentiation state of cells.
肝细胞核因子4α（HNF-4α）是一种转录因子，它控制胚胎肝脏发育，并维持和调节成年肝细胞中的基因表达。我们之前已经证明，HNF-4α的瞬时过表达会上调肝癌细胞系中一些肝脏特异性基因。在本研究中，我们通过评估HNF-4α在调节原代大鼠肝细胞的细胞活力和肝脏特异性功能中的作用来扩展这些研究。在用携带大鼠HNF-4α cDNA的腺病毒载体转染的细胞中，在长期培养过程中观察到肝脏特异性基因和功能的诱导和维持，这可能与防止线粒体膜电位的快速丧失有关。此外，我们证明转甲状腺素蛋白mRNA在原代肝细胞中被HNF-4α上调，但在肝癌细胞中则不然。这些结果表明，HNF-4α在维持形态和生化功能正常的肝细胞中发挥作用，并且HNF-4α诱导的肝脏特异性基因表达差异可能取决于细胞的分化状态。
