Search results for "Hepatocyte nuclear factor 4 alpha"
showing 5 items of 5 documents
Re-expression of C/EBP alpha induces CYP2B6, CYP2C9 and CYP2D6 genes in HepG2 cells.
1998
Cytochrome P450 (CYP) activity is very low or even absent in human hepatomas, a phenomenon that is accompanied by low levels of some liver transcription factors, notably C/EBP alpha. To investigate a possible link between this transcription factor and hepatic CYP expression, we have stably transfected HepG2 cells with a C/EBP alpha vector containing a Zn-inducible metallothionein promoter. Expression of functional C/EBP alpha up to liver levels concomitantly increased the mRNAs of several members of the CYP2 family (2B6, 2C9 and 2D6), suggesting that this transcription factor may play a relevant role in controlling the hepatic expression of CYP enzymes.
CCAAT/Enhancer-binding Protein α (C/EBPα) and Hepatocyte Nuclear Factor 4α (HNF4α) Synergistically Cooperate with Constitutive Androstane Receptor to…
2010
The transcription of tissue-specific and inducible genes is usually subject to the dynamic control of multiple activators. Dedifferentiated hepatic cell lines lose the expression of tissue-specific activators and many characteristic hepatic genes, such as drug-metabolizing cytochrome P450. Here we demonstrate that by combining adenoviral vectors for CCAAT/enhancer-binding protein α (C/EBPα), hepatocyte nuclear factor 4α (HNF4α), and constitutive androstane receptor, the CYP2B6 expression and inducibility by CITCO are restored in human hepatoma HepG2 cells at levels similar to those in cultured human hepatocytes. Moreover, several other phase I and II genes are simultaneously activated, whic…
Sequential Hepatogenic Transdifferentiation of Adipose Tissue-Derived Stem Cells: Relevance of Different Extracellular Signaling Molecules, Transcrip…
2009
Adipose tissue contains a mesenchymal stein cell (MSC) population Known as adipose-derived stein cells (ASCs) capable of differentiating into different cell types. Our aim was to induce hepatic transdifferentiation of ASCs by sequential exposure to several combinations of cytokines, growth factors, and hormones. The most efficient hepatogenic protocol includes fibroblastic growth factors (FGF) 2 and 4 and epidermal growth factor (EGF) (step 1), hepatocyte growth factor (HGF), FGF2, FGF4, and nicotinamide (Nic) (step 2), and oncostatin M (OSM), dexamethasone (Dex), and insulin-tranferrin-selenium (step 3). This protocol activated transcription factors [GATA6, Hex, CCAAT/enhancer binding prot…
Role of hepatocyte nuclear factor 3γ in the expression of human CYP2C genes
2004
Hepatocyte nuclear factor 3 gamma (HNF-3 gamma) is an important transcription factor for the maintenance of specific liver functions. However, its relevance in the expression of human cytochrome P450 (CYP) genes has not yet been explored. Several HNF3 putative binding sites can be identified in human CYP2C 5'-flanking regions. Gene reporter experiments with proximal promoters revealed that HNF-3 gamma transactivated CYP2C8, CYP2C9, and CYP2C19 (25-, 4-, and 4-fold, respectively), but it did not transactivate CYP2C18. However, overexpression of HNF-3 gamma in hepatoma cells by means of a recombinant adenovirus induced CYP2C9, CYP2C18, and CYP2C19 mRNA (4.5-, 20-, and 50-fold, respectively) b…
In vitro reprogramming of pancreatic alpha cells towards a beta cell phenotype following ectopic HNF4α expression
2015
There is currently a shortage of organ donors available for pancreatic beta cell transplantation into diabetic patients. An alternative source of beta cells is pre-existing pancreatic cells. While we know that beta cells can arise directly from alpha cells during pancreatic regeneration we do not understand the molecular basis for the switch in phenotype. The aim of the present study was to investigate if hepatocyte nuclear factor 4 alpha (HNF4α), a transcription factor essential for a normal beta cell phenotype, could induce the reprogramming of alpha cells towards potential beta cells. We utilised an in vitro model of pancreatic alpha cells, the murine αTC1-9 cell line. We initially chara…