Adenovirus-mediated hepatocyte nuclear factor-4alpha overexpression maintains liver phenotype in cultured rat hepatocytes.
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.
Naiki
Takafumi
T
Department of Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
Nagaki
Masahito
M
Asano
Takahiko
T
Kimata
Takayuki
T
Moriwaki
Hisataka
H
D000256:Adenoviridae / Q000235:genetics*; D000641:Ammonia / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation; D002470:Cell Survival; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D005840:Gentian Violet / Q000494:pharmacology; D051557:Hepatocyte Nuclear Factor 4; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008564:Membrane Potentials; D008858:Microscopy, Phase-Contrast; D008928:Mitochondria / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; D010750:Phosphoproteins; D014157:Transcription Factors; D000641:Ammonia; D001616:beta-Galactosidase; D005840:Gentian Violet