Search results for "Hepatocyte nuclear factor 4"

showing 10 items of 20 documents

Functional characterization of a peroxisome proliferator response-element located in the intron 3 of rat peroxisomal thiolase B gene.

2003

Expression of the rat peroxisomal 3-ketoacyl-CoA thiolase gene B is induced by peroxisome proliferators. Although a sequence element like a peroxisome proliferator-activated receptor (PPAR)-binding site is located in the promoter region of this gene, we previously found that this element is competent for the activation by hepatocyte nuclear factor-4, but not functional with PPARalpha. We describe here a new peroxisome proliferator-response element located in the intron 3 (+1422/+1434) that binds in vitro the PPARalpha/retinoid X receptor alpha heterodimer and confers the induction by PPARalpha in transfection assays. We propose a model of regulation of the rat thiolase B gene involving thos…

Peroxisome proliferator-activated receptor gammaResponse elementBiophysicsPeroxisome proliferator-activated receptorReceptors Cytoplasmic and NuclearRetinoid X receptorBiochemistryGene Expression Regulation EnzymologicStructure-Activity RelationshipPeroxisomesAnimalsAcetyl-CoA C-AcetyltransferaseMolecular BiologyCells Culturedchemistry.chemical_classificationThiolaseChemistryCell BiologyPhosphoproteinsMolecular biologyIntronsRatsDNA-Binding ProteinsBiochemistryHepatocyte Nuclear Factor 4LiverPeroxisome proliferator-activated receptor deltaPeroxisome ProliferatorsPeroxisome proliferator-activated receptor alphaPPARGC1BTranscription FactorsBiochemical and biophysical research communications
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PPARα/HNF4α Interplay on Diversified Responsive Elements. Relevance in the Regulation of Liver Peroxisomal Fatty Acid Catabolism

2012

In mammals, the liver is the major organ of fatty acid catabolism. This pathway is involved in both mitochondria and peroxisome. While mitochondria breaks down fatty acids with short, medium and long carbon chains, peroxisomes are involved in the catabolism of very long and branched chain fatty acids, which are degraded by three enzymes: acyl-CoA oxidase, multifunctional enzyme and thiolase enzyme. The active pathway results mainly from a tight transcriptional control of these gene-encoding enzymes. Two major nuclear receptors that are highly expressed in this organ are involved in this control, e.g. PPARα (peroxisome proliferator-activated receptor, α isoform) and HNF4α (hepatic nuclear fa…

Pharmacologychemistry.chemical_classificationFatty acid metabolismCatabolismThiolaseFatty AcidsClinical BiochemistryPeroxisome proliferator-activated receptorMetabolismPeroxisomeBiologyResponse Elementschemistry.chemical_compoundGene Expression RegulationHepatocyte Nuclear Factor 4LiverHepatocyte nuclear factor 4BiochemistrychemistryNuclear receptorPeroxisomesAnimalsHumansPPAR alphaCurrent Drug Metabolism
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Species-specific mechanisms for cholesterol 7alpha-hydroxylase (CYP7A1) regulation by drugs and bile acids.

2005

The gene encoding cholesterol 7alpha-hydroxylase (CYP7A1) is tightly regulated in order to control intrahepatic cholesterol and bile acid levels. Ligands of the xenobiotic-sensing pregnane X receptor inhibit CYP7A1 expression. To retrace the evolution of the molecular mechanisms underlying CYP7A1 inhibition, we used a chicken hepatoma cell system that retains the ability to be induced by phenobarbital and other drugs. Whereas bile acids regulate CYP7A1 via small heterodimer partner and liver receptor homolog-1, mRNA expression of these nuclear receptors is unchanged by xenobiotics. Instead, drugs repress chicken hepatic nuclear factor 4alpha (HNF4alpha) transcript levels concomitant with a …

Receptors Steroidmedicine.drug_classMolecular Sequence DataBiophysicsReceptors Cytoplasmic and NuclearBiologyIn Vitro TechniquesCholesterol 7 alpha-hydroxylaseBiochemistryGene Expression Regulation EnzymologicBile Acids and SaltsMiceSpecies SpecificitymedicineAnimalsHumansRNA MessengerCholesterol 7-alpha-HydroxylaseMolecular BiologyCells CulturedMice KnockoutPregnane X receptorBile acidLiver receptor homolog-1Pregnane X ReceptorPhosphoproteinsRecombinant ProteinsDNA-Binding ProteinsBiochemistryNuclear receptorHepatocyte Nuclear Factor 4PhenobarbitalSmall heterodimer partnerHepatocytesFarnesoid X receptorSignal transductionChickensSignal TransductionTranscription FactorsArchives of biochemistry and biophysics
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The peroxisome proliferator response element (PPRE) present at positions -681/-669 in the rat liver 3-ketoacyl-CoA thiolase B gene functionally inter…

2000

Although previous data showed that the putative thiolase B PPRE located at -681/-669 bind the PPARalpha-RXRalpha heterodimer in vitro (Kliewer et al. (1992) Nature 358, 771-774), there is no evidence about the functional role of this element. By gel mobility-shift assay, we found an interaction of this PPRE with not only PPARalpha but also with HNF-4. By transfection of cells with the putative PPRE-driven luciferase reporter vector and PPARalpha, we found no significant activation of the luciferase gene expression, in contrast to the case with reporter expression driven by the PPRE of the peroxisomal bifunctional enzyme. On the other hand, HNF-4 activated the luciferase gene expression driv…

Response elementBiophysicsReceptors Cytoplasmic and NuclearBiologyTransfectionBiochemistryDNA-binding proteinPeroxisomal Bifunctional EnzymeGenes ReporterGene expressionAnimalsMolecular BiologyGeneDNA PrimersBase SequenceThiolaseCell BiologyTransfectionDNAAcetyl-CoA C-AcyltransferasePhosphoproteinsMolecular biologyRatsDNA-Binding ProteinsHepatocyte nuclear factor 4Hepatocyte Nuclear Factor 4LiverCOS CellsPeroxisome ProliferatorsTranscription FactorsBiochemical and biophysical research communications
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Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4α upregulation in primary human hepatocytes

2013

Abstract Background Organic cation transporter 1 (OCT1, SLC22A1) is a membrane transporter that is important for therapeutic effect of the antidiabetic drug metformin. Its liver-specific expression in hepatocytes is strongly controlled by hepatocyte nuclear factor-4α (HNF4α). HNF4α expression and transcriptional activity have been demonstrated to be augmented by glucocorticoid receptor (GR) in human hepatocytes and rodent livers. Methods It was examined whether GR activation indirectly induces OCT1 gene expression via HNF4α up-regulation in primary human hepatocytes.We also examined which other transcription factors are involved in OCT1 gene expression and whether they are regulated by dexa…

Time FactorsPrimary Cell CultureTransfectionDexamethasoneReceptors GlucocorticoidGlucocorticoid receptorTransduction GeneticEnhancer bindingCoactivatorGene expressionHumansRNA MessengerGlucocorticoidsTranscription factorPharmacologyRegulation of gene expressionChemistryCCAAT-Enhancer-Binding Protein-betaOrganic Cation Transporter 1Hep G2 CellsGeneral MedicineTransfectionPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaMolecular biologyUp-RegulationHepatocyte Nuclear Factor 4Cell cultureHepatocytesTranscription FactorsPharmacological Reports
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The stable repression of mesenchymal program is required for hepatocyte identity: A novel role for hepatocyte nuclear factor 4α

2011

The concept that cellular terminal differentiation is stably maintained once development is complete has been questioned by numerous observations showing that differentiated epithelium may undergo an epithelial-to-mesenchymal transition (EMT) program. EMT and the reverse process, mesenchymal-to-epithelial transition (MET), are typical events of development, tissue repair, and tumor progression. In this study, we aimed to clarify the molecular mechanisms underlying these phenotypic conversions in hepatocytes. Hepatocyte nuclear factor 4α (HNF4α) was overexpressed in different hepatocyte cell lines and the resulting gene expression profile was determined by real-time quantitative polymerase…

Transcription FactorCellular differentiationMESH: Mice KnockoutMESH: HepatocytesMesodermMice0302 clinical medicineMESH: Liver NeoplasmsMESH: AnimalsHepatocyteHepatocyte Nuclear Factor 1-alphaMESH: Carcinoma HepatocellularRegulator geneHepatocyte differentiationMice KnockoutMESH: Mesoderm0303 health sciencesLiver NeoplasmsCell DifferentiationMESH: Transcription FactorsCell biologyHepatocyte nuclear factorsPhenotypeMESH: Models AnimalHepatocyte Nuclear Factor 4MESH: Epithelial CellsLiver Neoplasm030220 oncology & carcinogenesisModels AnimalMESH: Hepatocyte Nuclear Factor 4HumanMESH: Cell DifferentiationMESH: Cell Line TumorCarcinoma Hepatocellular[SDV.BC]Life Sciences [q-bio]/Cellular BiologyBiologyMESH: PhenotypeArticle03 medical and health scienceshepatocyte; mesenchymal program; SnailCell Line TumorAnimalsHumansMESH: Hepatocyte Nuclear Factor 1-alphaMESH: MiceTranscription factorAnimals; Carcinoma Hepatocellular; Cell Differentiation; Cell Line Tumor; Epithelial Cells; Hepatocyte Nuclear Factor 1-alpha; Hepatocyte Nuclear Factor 4; Hepatocytes; Humans; Liver Neoplasms; Mesoderm; Mice; Mice Knockout; Models Animal; Phenotype; Snail Family Transcription Factors; Transcription Factors; Hepatology030304 developmental biologyEpithelial CellMESH: HumansHepatologyAnimalMesenchymal stem cellEpithelial CellsSnail Family Transcription FactorMolecular biologyHepatocyte nuclear factor 4HepatocytesSnail Family Transcription FactorsChromatin immunoprecipitationTranscription Factors
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An epistatic mini-circuitry between the transcription factors Snail and HNF4α controls liver stem cell and hepatocyte features exhorting opposite reg…

2011

Preservation of the epithelial state involves the stable repression of epithelial-to-mesenchymal transition program, whereas maintenance of the stem compartment requires the inhibition of differentiation processes. A simple and direct molecular mini-circuitry between master elements of these biological processes might provide the best device to keep balanced such complex phenomena. In this work, we show that in hepatic stem cell Snail, a transcriptional repressor of the hepatocyte differentiation master gene HNF4α, directly represses the expression of the epithelial microRNAs (miRs)-200c and-34a, which in turn target several stem cell genes. Notably, in differentiated hepatocytes HNF4α, p…

Transcription GeneticTranscription FactorCellular differentiationLiver Stem CellSnailMESH: Mice KnockoutMESH: HepatocytesMice0302 clinical medicineSnail; hnf4a; mir-200; mir-34a; stemness; hepatocyte differentiationHepatocyteMESH: AnimalsMice KnockoutHepatocyte differentiationmir-34a0303 health sciencesStemneStem CellsMicroRNACell DifferentiationMESH: Transcription FactorsCell biologySnailmir-200Hepatocyte Nuclear Factor 4Liver030220 oncology & carcinogenesisMiRs-200MESH: Hepatocyte Nuclear Factor 4Hepatocyte differentiation; HNF4a; MiR-34a; MiRs-200; Snail; Stemness; Animals; Cell Differentiation; Epithelial-Mesenchymal Transition; Hepatocyte Nuclear Factor 4; Hepatocytes; Liver; Mice; Mice Knockout; MicroRNAs; Snail Family Transcription Factors; Stem Cells; Transcription Factors; Transcription Genetic; Cell Biology; Molecular BiologyStem cellhnf4aMESH: Cell Differentiationhepatocyte differentiationEpithelial-Mesenchymal TransitionMESH: Stem Cells[SDV.BC]Life Sciences [q-bio]/Cellular BiologyBiologystemness03 medical and health sciencesStem Cellbiology.animalAnimals[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular BiologyEpithelial–mesenchymal transitionMESH: MiceMolecular BiologyTranscription factor030304 developmental biologyOriginal PaperAnimalMESH: Transcription GeneticSnail Family Transcription FactorCell BiologyMolecular biologyMicroRNAsMESH: Epithelial-Mesenchymal TransitionHepatocyte nuclear factor 4HepatocytesSnail Family Transcription FactorsMESH: MicroRNAsMESH: LiverTranscription FactorsCell Death & Differentiation
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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…

Transcriptional ActivationRecombinant Fusion ProteinsGenetic VectorsBiophysicsBiologyHydroxamic AcidsTransfectionBiochemistryGene Expression Regulation EnzymologicAdenoviridaeCytochrome P-450 Enzyme SystemSp3 transcription factorCell Line TumormedicineHumansRNA MessengerEnzyme InhibitorsLuciferasesPromoter Regions GeneticMolecular BiologyTranscription factorBinding SitesNuclear ProteinsPromoterMolecular biologyDNA-Binding ProteinsHistone Deacetylase InhibitorsHepatocyte nuclear factorsTrichostatin AHepatocyte nuclear factor 4Hepatocyte nuclear factor 4 alphaHepatocytesFOXA2Transcription Initiation SiteHepatocyte Nuclear Factor 3-gammaHeLa CellsTranscription Factorsmedicine.drugArchives of Biochemistry and Biophysics
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TGFβ-induced EMT requires focal adhesion kinase (FAK) signaling

2007

The epithelial-to-mesenchymal transition (EMT) is a crucial process, occurring both during development and tumor progression, by which an epithelial cell undergoes a conversion to a mesenchymal phenotype, dissociates from initial contacts and migrates to secondary sites. We recently reported that in hepatocytes the multifunctional cytokine TGFβ induces a full EMT characterized by (i) Snail induction, (ii) E-cadherin delocalization and down-regulation, (iii) down-regulation of the hepatocyte transcriptional factor HNF4α and (iv) up-regulation of mesenchymal and invasiveness markers. In particular, we showed that Snail directly causes the transcriptional down-regulation of E-cadherin and HN…

Transcriptional ActivationTGFβFAK; MT; Src; TGFβ; Animals; Biomarkers Tumor; Cadherins; Cell Line; Cell Transformation Neoplastic; Enzyme Activation; Epithelial Cells; Focal Adhesion Protein-Tyrosine Kinases; Hepatocytes; Liver Neoplasms; Mesoderm; Mice; Neoplasm Invasiveness; Signal Transduction; Transcriptional Activation; Transforming Growth Factor beta; Up-Regulation; src-Family Kinases; Cell BiologyCell LineMesodermFocal adhesionMiceTransforming Growth Factor betaBiomarkers TumorAnimalsHepatocyteNeoplasm InvasivenessNeoplasm InvasiveneEpithelial CellFocal Adhesion Protein-Tyrosine KinaseFAKbiologyAnimalCadherinLiver NeoplasmsMesenchymal stem cellEpithelial CellsCell BiologyTransforming growth factor betaTgf beta; fak; srcCadherinsUp-RegulationCell biologyEnzyme ActivationCell Transformation Neoplasticsrc-Family KinasesHepatocyte nuclear factor 4Liver NeoplasmTumor progressionMTFocal Adhesion Protein-Tyrosine KinasesCadherinHepatocytesCancer researchbiology.proteinsrc-Family KinaseSignal transductionSrcSignal TransductionProto-oncogene tyrosine-protein kinase SrcExperimental Cell Research
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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…

medicine.medical_specialtyBiologyBiochemistryAlpha cellCell LineMiceEndocrinologyInsulin-Secreting CellsInternal medicinemedicineAnimalspancreatic alpha cellsMolecular Biologyreprogramming3T3-L1Cellular ReprogrammingAntigens Differentiationbeta cellCell biologyEndocrinologyHepatocyte Nuclear Factor 4Glucagon-Secreting CellsCell cultureHepatocyte nuclear factor 4 alphaPAX4Ectopic expressionBeta cellReprogrammingMolecular and Cellular Endocrinology
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