ArticleToxicological sciences : an official journal of the Society of Toxicology2010
Alterations in hepatic mRNA expression of phase II enzymes and xenobiotic transporters after targeted disruption of hepatocyte nuclear factor 4 alpha.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 67 citations in OpenAlex.
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- Crosstalk of hepatocyte nuclear factor 4a and glucocorticoid receptor in the regulation of lipid metabolism in mice fed a high-fat-high-sugar diet.Lipids in health and disease · 2022Article
- Gestational Exposure to Ultrafine Particles Reveals Sex- and Dose-Specific Changes in Offspring Birth Outcomes, Placental Morphology, and Gene Networks.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- RORα phosphorylation by casein kinase 1α as glucose signal to regulate estrogen sulfation in human liver cells.The Biochemical journal · 2020Article
- Novel insights into the organic solute transporter alpha/beta, OSTα/β: From the bench to the bedside.Pharmacology & therapeutics · 2020Review
- Hepatocyte nuclear factor 4α negatively regulates connective tissue growth factor during liver regeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Enhanced Intestinal Permeability and Plasma Concentration of Metformin in Rats by the Repeated Administration of Red Ginseng Extract.Pharmaceutics · 2019Article
- The regulation of drug-metabolizing enzymes and membrane transporters by inflammation: Evidences in inflammatory diseases and age-related disorders.Journal of food and drug analysis · 2019Review
- Age-associated changes in GSH S-transferase gene/proteins in livers of rats.Redox report : communications in free radical research · 2018Article
- Expression of MATE1, P-gp, OCTN1 and OCTN2, in epithelial and immune cells in the lung of COPD and healthy individuals.Respiratory research · 2018Article
- Characterization of OATP1B3 and OATP2B1 transporter expression in the islet of the adult human pancreas.Histochemistry and cell biology · 2017Article
- Regulation of hepatic microRNA expression by hepatocyte nuclear factor 4 alpha.World journal of hepatology · 2017Article
- Crosstalk of HNF4Acta pharmaceutica Sinica. B · 2016Review
- Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.Hepatology (Baltimore, Md.) · 2016Article
- Molecular mechanisms underlying the enhanced functions of three-dimensional hepatocyte aggregates.Biomaterials · 2014Article
- Article
- Regulation of hepatic phase II metabolism in pregnant mice.The Journal of pharmacology and experimental therapeutics · 2013Article
- Effect of graded Nrf2 activation on phase-I and -II drug metabolizing enzymes and transporters in mouse liver.PloS one · 2012Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocyte nuclear factor 4 alpha (HNF4a) is a liver-enriched master regulator of liver function. HNF4a is important in regulating hepatic expression of certain cytochrome P450s. The purpose of this study was to use mice lacking HNF4a expression in liver (HNF4a-HNull) to elucidate the role of HNF4a in regulating hepatic expression of phase II enzymes and transporters in mice. Compared with male wild-type mice, HNF4a-HNull male mouse livers had (1) markedly lower messenger RNAs (mRNAs) encoding the uptake transporters sodium taurocholate cotransporting polypeptide, organic anion transporting polypeptide (Oatp) 1a1, Oatp2b1, organic anion transporter 2, sodium phosphate cotransporter type 1, sulfate anion transporter 1, sodium-dependent vitamin C transporter 1, the phase II enzymes Uridine 5'-diphospho (UDP)-glucuronosyltransferase (Ugt) 2a3, Ugt2b1, Ugt3a1, Ugt3a2, sulfotransferase (Sult) 1a1, Sult1b1, Sult5a1, the efflux transporters multidrug resistance-associated protein (Mrp) 6, and multidrug and toxin extrusion 1; (2) moderately lower mRNAs encoding Oatp1b2, organic cation transporter (Oct) 1, Ugt1a5, Ugt1a9, glutathione S-transferase (Gst) m4, Gstm6, and breast cancer resistance protein; but (3) higher mRNAs encoding Oatp1a4, Octn2, Ugt1a1, Sult1e1, Sult2a2, Gsta4, Gstm1-m3, multidrug resistance protein (Mdr) 1a, Mrp3, and Mrp4. Hepatic signaling of nuclear factor E2-related factor 2 and pregnane X receptor appear to be activated in HNF4a-HNull mice. In conclusion, HNF4a deficiency markedly alters hepatic mRNA expression of a large number of phase II enzymes and transporters, probably because of the loss of HNF4a, which is a transactivator and a determinant of gender-specific expression and/or adaptive activation of signaling pathways important in hepatic regulation of these phase II enzymes and transporters.
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