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Children's Health Research Institute, London, Ontario, Canada
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Children's Health Research Institute, London, Ontario, Canada
Department of Pediatrics, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada
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of glucose. However, during prolonged periods of glucose starvation, gluconeogenesis is induced in fetal hepatocytes ( Joyner et al. 2016 ). Indeed, increased fetal liver expression of gluconeogenic enzymes has been reported in several animal models
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI, USA
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Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA
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on the role of insulin in liver development; maternal nutrition and fetal programing as they affect liver physiology; and the application of the fetal hepatocyte phenotype to cell-based therapy for liver disease. We focus, in part, on our own work on
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ABSTRACT
In McA-RH 8994 rat hepatoma cells, all-transretinoic acid (t-RA) induces expression of the α-fetoprotein (AFP) and albumin genes and results in a phenotype similar to differentiated fetal hepatocytes. The present study elucidated the mechanism involved in AFP gene regulation mediated by retinoic acid. Northern blot analyses demonstrated that 9-cis-retinoic acid (c-RA), a ligand for retinoid x receptors (RXRs), also induced expression of the AFP gene in McA-RH 8994 cells. The induction was time- and dose-dependent. Northern blots and transfection assays using the 7·3 kb full-length regulatory region of the AFP gene demonstrated that c-RA was more effective than t-RA in regulating expression of the AFP gene. At 10−7 m, c-RA increased AFP mRNA 5-fold and chloramphenicol acetyltransferase (CAT) activity 2·5-fold. In contrast, t-RA at a concentration of 10−7 m exerted no significant effect; 10− 6 to 10−5 m t-RA was needed to affect AFP gene expression. These data suggested that activation of RXRs is essential for the regulation of the AFP gene. Co-transfection experiments revealed that overexpression of RXRα in McA-RH 8994 cells further enhanced the CAT activity induced by c-RA. In addition, c-RA did not alter the half-life of AFP mRNA. Thus, RXRα may play a crucial role in transcriptional regulation of the AFP gene and in controlling hepatocyte phenotype.
Metabolism and Cancer Laboratory, Physiology, Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia Departments of
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Metabolism and Cancer Laboratory, Physiology, Prince Henry's Institute of Medical Research, Clayton, Victoria 3168, Australia Departments of
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ER 1995a Characterization of the sequences of the human CYP19 (aromatase) gene that mediate regulation by glucocorticoids in adipose stromal cells and fetal hepatocytes . Molecular Endocrinology 9 340 – 349 . ( doi:10.1210/me.9.3.340 ). Zhao
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Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM) and Institut du cancer de Montréal, Department of Medicine, Université de Montréal, Montréal, Québec, Canada
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). Spatial–temporal distribution therefore places GATA-1, GATA-4, and GATA-6 as mediators of basal transcription of hepcidin in fetal hepatocytes while GATA-6 as the mediator in postnatal hepatocytes. GATA proteins regulate other genes through functional
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G 1998 Development and regulation of glucose-6-phosphatase gene expression in rat liver, intestine, and kidney: in vivo and in vitro studies in cultured fetal hepatocytes. Diabetes 47 882 –889. Chen R , Meseck M
07743 Jena, Germany
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07743 Jena, Germany
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07743 Jena, Germany
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07743 Jena, Germany
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07743 Jena, Germany
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the sequences of the human CYP19 (aromatase) gene that mediate regulation by glucocorticoids in adipose stromal cells and fetal hepatocytes . Molecular Endocrinology 9 340 – 349 . ( doi:10.1210/me.9.3.340 ). Zhao Y Nichols JE Bulun SE
Institute for Research and Innovation in Health (I3S), University of Porto, Porto, Portugal
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Institute for Research and Innovation in Health (I3S), University of Porto, Porto, Portugal
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Institute for Research and Innovation in Health (I3S), University of Porto, Porto, Portugal
Medical Faculty, University of Porto, Porto, Portugal
Department of Pathology, Centro Hospitalar S. João, Porto, Portugal
Department of Pathology, Medical Faculty, University of Porto, Porto, Portugal
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Institute for Research and Innovation in Health (I3S), University of Porto, Porto, Portugal
Medical Faculty, University of Porto, Porto, Portugal
Department of Pathology, Medical Faculty, University of Porto, Porto, Portugal
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Lutgehetmann M Dierlamm J Lohse AW Brummendorf TH 2011 Forced activation of beta-catenin signaling supports the transformation of hTERT-immortalized human fetal hepatocytes . Molecular Cancer Research 9 1222 – 1231 . ( doi:10
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Mendelson CR Simpson ER 1995a Characterization of the sequences of the human CYP19 (aromatase) gene that mediate regulation by glucocorticoids in adipose stromal cells and fetal hepatocytes. Molecular Endocrinology 9 340 – 349 . Zhao Y
