419
Views
0
CrossRef citations to date
0
Altmetric
Review Articles

A transcriptional regulatory network of HNF4α and HNF1α involved in human diseases and drug metabolism

, , &
Pages 361-385 | Received 03 May 2022, Accepted 14 Jul 2022, Published online: 26 Jul 2022

References

  • Ahmed M, Cheng M, Cheung IY, Cheung NK. 2015. Human derived dimerization tag enhances tumor killing potency of a T-cell engaging bispecific antibody. Oncoimmunology. 4(4):e989776.
  • Armendariz AD, Krauss RM. 2009. Hepatic nuclear factor 1- alpha: inflammation, genetics, and atherosclerosis. Curr Opin Lipidol. 20(2):106–111.
  • Aueviriyavit S, Furihata T, Morimoto K, Kobayashi K, Chiba K. 2007. Hepatocyte nuclear factor 1 alpha and 4 alpha are factors involved in interindividual variability in the expression of UGT1A6 and UGT1A9 but not UGT1A1, UGT1A3 and UGT1A4 mRNA in human livers. Drug Metab Pharmacokinet. 22(5):391–398.
  • Babeu JP, Boudreau F. 2014. Hepatocyte nuclear factor 4-alpha involvement in liver and intestinal inflammatory networks. World J Gastroenterol. 20(1):22–30.
  • Barbier O, Girard H, Inoue Y, Duez H, Villeneuve L, Kamiya A, Fruchart JC, Guillemette C, Gonzalez FJ, Staels B. 2005. Hepatic expression of the UGT1A9 gene is governed by hepatocyte nuclear factor 4α. Mol Pharmacol. 67(1):241–249.
  • Begum S. 2020. Hepatic nuclear factor 1 alpha (HNF-1α) in human physiology and molecular medicine. Curr Mol Pharmacol. 13(1):50–56.
  • Bélanger AS, Tojcic J, Harvey M, Guillemette C. 2010. Regulation of UGT1A1 and HNF1 transcription factor gene expression by DNA methylation in colon cancer cells. BMC Mol Biol. 11:9.
  • Beysel S, Pinarli FA, Eyerci N, Kizilgul M, Hepsen S, Alhan A, Kan S, Caliskan M, Bozkurt E, Cakal E. 2020. HNF1A gene p.I27L is associated with co-existing preeclampsia in gestational diabetes mellitus. Gynecol Endocrinol. 36(6):530–534.
  • Bi Y, Wang Y, Xie W. 2019. The interplay between hepatocyte nuclear factor 4α (HNF4α) and cholesterol sulfotransferase (SULT2B1b) in hepatic energy homeostasis. Liver Res. 3(3–4):143–149.
  • Bioulac-Sage P, Blanc JF, Rebouissou S, Balabaud C, Zucman-Rossi J. 2007. Genotype phenotype classification of hepatocellular adenoma. World J Gastroenterol. 13(19):2649–2654.
  • Bisceglia F, Battistelli C, Noce V, Montaldo C, Zammataro A, Strippoli R, Tripodi M, Amicone L, Marchetti A. 2019. TGFbeta impairs HNF1alpha functional activity in epithelial-to-mesenchymal transition interfering with the recruitment of CBP/p300 acetyltransferases. Front Pharmacol. 10:942.
  • Boj SF, Servitja JM, Martin D, Rios M, Talianidis I, Guigo R, Ferrer J. 2009. Functional targets of the monogenic diabetes transcription factors HNF-1alpha and HNF-4alpha are highly conserved between mice and humans. Diabetes. 58(5):1245–1253.
  • Bonzo JA, Patterson AD, Krausz KW, Gonzalez FJ. 2010. Metabolomics identifies novel Hnf1α-Dependent physiological pathways in vivo. Mol Endocrinol. 24(12):2343–2355.
  • Chamouton J, Latruffe N. 2012. PPARα/HNF4α interplay on diversified responsive elements. Relevance in the regulation of liver peroxisomal fatty acid catabolism. Curr Drug Metab. 13(10):1436–1453.
  • Chang HR, Nam S, Kook MC, Kim KT, Liu X, Yao H, Jung HR, Lemos RJ, Seo HH, Park HS, et al. 2016. HNF4α is a therapeutic target that links AMPK to WNT signalling in early-stage gastric cancer. Gut. 65(1):19–32.
  • Chen L, Bao Y, Jiang S, Zhong XB. 2020. The roles of long noncoding RNAs HNF1α-AS1 and HNF4α-AS1 in drug metabolism and human diseases. ncRNA. 6(2):24.
  • Chen L, Bao Y, Piekos SC, Zhu K, Zhang L, Zhong XB. 2018. A transcriptional regulatory network containing nuclear receptors and long noncoding RNAs controls basal and drug-induced expression of cytochrome p450s in HepaRG cells. Mol Pharmacol. 94(1):749–759.
  • Cheung C, Akiyama TE, Kudo G, Gonzalez FJ. 2003. Hepatic expression of cytochrome P450s in hepatocyte nuclear factor 1-alpha (HNF1alpha)-deficient mice. Biochem Pharmacol. 66(10):2011–2020.
  • Chiang JY. 2009. Hepatocyte nuclear factor 4α regulation of bile acid and drug metabolism. Expert Opin Drug Metab Toxicol. 5(2):137–147.
  • Chiang TS, Yang KC, Chiou LL, Huang GT, Lee HS. 2014. Enhancement of CYP3A4 activity in Hep G2 cells by lentiviral transfection of hepatocyte nuclear factor-1 alpha. PLOS One. 9(4):e94885.
  • Chung I, Bresnick E. 1997. Identification of positive and negative regulatory elements of the human cytochrome P4501A2 (CYP1A2) gene. Arch Biochem Biophys. 338(2):220–226.
  • Colleypriest BJ, Burke ZD, Griffiths LP, Chen Y, Yu WY, Jover R, Bock M, Biddlestone L, Quinlan JM, Ward SG, et al. 2017. Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium. Differentiation. 93:39–49.
  • Congiu M, Mashford ML, Slavin JL, Desmond PV. 2009. Coordinate regulation of metabolic enzymes and transporters by nuclear transcription factors in human liver disease. J Gastroenterol Hepatol. 24(6):1038–1044.
  • Cubuk H, Yalcin CO. 2021. A review of functional characterization of single amino acid change mutations in HNF transcription factors in MODY pathogenesis. Protein J. 40(3):348–360.
  • Cusato J, De Nicolo A, Boglione L, Favata F, Ariaudo A, Mornese PS, Carcieri C, Guido F, Avataneo V, Cariti G, et al. 2018. Pharmacogenetics of the anti-HCV drug sofosbuvir: a preliminary study. J Antimicrob Chemother. 73(6):1659–1664.
  • Cusato J, De Nicolo A, Boglione L, Favata F, Ariaudo A, Mornese PS, Guido F, Avataneo V, Carcieri C, Cariti G, et al. 2017. Influence of ABCB11 and HNF4α genes on daclatasvir plasma concentration: preliminary pharmacogenetic data from the Kineti-C study. J Antimicrob Chemother. 72(10):2846–2849.
  • Dai X, Zhang W, Zhang H, Sun S, Yu H, Guo Y, Kou Z, Zhao G, Du L, Jiang S, et al. 2014. Modulation of HBV replication by microRNA-15b through targeting hepatocyte nuclear factor 1α. Nucleic Acids Res. 42(10):6578–6590.
  • Del PS, Erkelens DW, Leutenegger M. 2003. Six-month efficacy of benfluorex vs. placebo or metformin in diet-failed type 2 diabetic patients. Acta Diabetol. 40(1):20–27.
  • Dietrich CG, Martin IV, Porn AC, Voigt S, Gartung C, Trautwein C, Geier A. 2007. Fasting induces basolateral uptake transporters of the SLC family in the liver via HNF4alpha and PGC1alpha. Am J Physiol Gastrointest Liver Physiol. 293(3):G585–G590.
  • Ding X, Lichti K, Kim I, Gonzalez FJ, Staudinger JL. 2006. Regulation of constitutive androstane receptor and its target genes by fasting, cAMP, hepatocyte nuclear factor alpha, and the coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha. J Biol Chem. 281(36):26540–26551.
  • Dluzen DF, Lazarus P. 2015. MicroRNA regulation of the major drug-metabolizing enzymes and related transcription factors. Drug Metab Rev. 47(3):320–334.
  • Duan Y, Zhu J, Yang J, Gu W, Bai X, Liu G, Xiangyang L. 2021. A decade's review of miRNA: a center of transcriptional regulation of drug-metabolizing enzymes and transporters under hypoxia. Curr Drug Metab. 22(9):709–725.
  • Echchgadda I, Song CS, Oh T, Ahmed M, De La Cruz IJ, Chatterjee B. 2007. The xenobiotic-sensing nuclear receptors pregnane X receptor, constitutive androstane receptor, and orphan nuclear receptor hepatocyte nuclear factor 4α in the regulation of human steroid-/bile acid-sulfotransferase. Mol Endocrinol. 21(9):2099–2111.
  • Ehmer U, Kalthoff S, Lankisch TO, Freiberg N, Manns MP, Strassburg CP. 2010. Shared regulation of UGT1A7 by hepatocyte nuclear factor (HNF) 1alpha and HNF4alpha. Drug Metab Dispos. 38(7):1246–1257.
  • Florentino RM, Fraunhoffer NA, Morita K, Takeishi K, Ostrowska A, Achreja A, Animasahun O, Haep N, Arazov S, Agarwal N, et al. 2020. Cellular location of HNF4α is linked with terminal liver failure in humans. Hepatol Commun. 4(6):859–875.
  • Forlani G, Zucchini S, Di Rocco A, Di Luzio R, Scipione M, Marasco E, Romeo G, Marchesini G, Mantovani V. 2010. Double heterozygous mutations involving both HNF1A/MODY3 and HNF4A/MODY1 genes: a case report. Diabetes Care. 33(11):2336–2338.
  • Furihata T, Satoh T, Yamamoto N, Kobayashi K, Chiba K. 2007. Hepatocyte nuclear factor 1 alpha is a factor responsible for the interindividual variation of OATP1B1 mRNA levels in adult Japanese livers. Pharm Res. 24(12):2327–2332.
  • Gamou T, Habano W, Terashima J, Ozawa S. 2015. A CAR-responsive enhancer element locating approximately 31 kb upstream in the 5'-flanking region of rat cytochrome P450 (CYP) 3A1 gene. Drug Metab Pharmacokinet. 30(2):188–197.
  • Gao X, Sanderson SM, Dai Z, Reid MA, Cooper DE, Lu M, Richie JJ, Ciccarella A, Calcagnotto A, Mikhael PG, et al. 2019. Dietary methionine influences therapy in mouse cancer models and alters human metabolism. Nature. 572(7769):397–401.
  • Gao Y, Yan Y, Guo J, Zhang Q, Bi D, Wang F, Chang Z, Lu L, Yao X, Wei Q. 2019. HNF-4α downregulation promotes tumor migration and invasion by regulating E-cadherin in renal cell carcinoma. Oncol Rep. 42(3):1066–1074.
  • Gardner-Stephen DA, Mackenzie PI. 2007. Hepatocyte nuclear factor1 transcription factors are essential for the UDP-glucuronosyltransferase 1A9 promoter response to hepatocyte nuclear factor 4α. Pharmacogenet Genomics. 17(1):25–36.
  • Gardner-Stephen DA, Mackenzie PI. 2007. Isolation of the UDP-glucuronosyltransferase 1A3 and 1A4 proximal promoters and characterization of their dependence on the transcription factor hepatocyte nuclear factor 1α. Drug Metab Dispos. 35(1):116–120.
  • Gardner-Stephen DA, Mackenzie PI. 2008. Liver-enriched transcription factors and their role in regulating UDP glucuronosyltransferase gene expression. Curr Drug Metab. 9(5):439–452.
  • Garrison WD, Battle MA, Yang C, Kaestner KH, Sladek FM, Duncan SA. 2006. Hepatocyte nuclear factor 4α is essential for embryonic development of the mouse colon. Gastroenterology. 130(4):1207–1220.
  • Geier A, Dietrich CG, Voigt S, Ananthanarayanan M, Lammert F, Schmitz A, Trauner M, Wasmuth HE, Boraschi D, Balasubramaniyan N, et al. 2005. Cytokine-dependent regulation of hepatic organic anion transporter gene transactivators in mouse liver. Am J Physiol Gastrointest Liver Physiol. 289(5):G831–G841.
  • Geier A, Zollner G, Dietrich CG, Wagner M, Fickert P, Denk H, van Rooijen N, Matern S, Gartung C, Trauner M. 2005. Cytokine-independent repression of rodent Ntcp in obstructive cholestasis. Hepatology. 41(3):470–477.
  • Girard R, Darsigny M, Jones C, Maloum-Rami F, Gelinas Y, Carpentier AC, Laplante M, Perreault N, Boudreau F. 2019. HNF4α is a novel regulator of intestinal glucose-dependent insulinotropic polypeptide. Sci Rep. 9(1):4200.
  • Godoy P, Schmidt-Heck W, Natarajan K, Lucendo-Villarin B, Szkolnicka D, Asplund A, Bjorquist P, Widera A, Stober R, Campos G, et al. 2015. Gene networks and transcription factor motifs defining the differentiation of stem cells into hepatocyte-like cells. J Hepatol. 63(4):934–942.
  • Gonzalez FJ. 2008. Regulation of hepatocyte nuclear factor 4 alpha-mediated transcription. Drug Metab Pharmacokinet. 23(1):2–7.
  • Gregory PA, Hansen AJ, Mackenzie PI. 2000. Tissue specific differences in the regulation of the UDP glucuronosyltransferase 2B17 gene promoter. Pharmacogenetics. 10(9):809–820.
  • Gregory PA, Lewinsky RH, Gardner-Stephen DA, Mackenzie PI. 2004. Coordinate regulation of the human UDP-glucuronosyltransferase 1A8, 1A9, and 1A10 genes by hepatocyte nuclear factor 1α and the caudal-related homeodomain protein 2. Mol Pharmacol. 65(4):953–963.
  • Gregory PA, Lewinsky RH, Gardner-Stephen DA, Mackenzie PI. 2004. Regulation of UDP glucuronosyltransferases in the gastrointestinal tract. Toxicol Appl Pharmacol. 199(3):354–363.
  • Gregory PA, Mackenzie PI. 2002. The homeodomain Pbx2-Prep1 complex modulates hepatocyte nuclear factor 1alpha-mediated activation of the UDP-glucuronosyltransferase 2B17 gene. Mol Pharmacol. 62(1):154–161.
  • Grimm AA, Brace CS, Wang T, Stormo GD, Imai S. 2011. A nutrient-sensitive interaction between Sirt1 and HNF-1α regulates CRP expression. Aging Cell. 10(2):305–317.
  • Griscelli F, Ezanno H, Soubeyrand M, Feraud O, Oudrhiri N, Bonnefond A, Turhan AG, Froguel P, Bennaceur-Griscelli A. 2018. Generation of an induced pluripotent stem cell (iPSC) line from a patient with maturity-onset diabetes of the young type 3 (MODY3) carrying a hepatocyte nuclear factor 1-alpha (HNF1A) mutation. Stem Cell Res. 29:56–59.
  • Gu XQ, Tang D, Wan P, Qin T, Yang TH, Wu J, Ji H, Liu JC, Xue F, Tang YJ, et al. 2021. Multiple microRNAs regulate tacrolimus metabolism through CYP3A5. Pharmacol Res. 164:105382.
  • Gupta RK, Kaestner KH. 2004. HNF-4alpha: from MODY to late-onset type 2 diabetes. Trends Mol Med. 10(11):521–524.
  • Gupta RK, Vatamaniuk MZ, Lee CS, Flaschen RC, Fulmer JT, Matschinsky FM, Duncan SA, Kaestner KH. 2005. The MODY1 gene HNF-4alpha regulates selected genes involved in insulin secretion. J Clin Invest. 115(4):1006–1015.
  • Hayhurst GP, Lee YH, Lambert G, Ward JM, Gonzalez FJ. 2001. Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol. 21(4):1393–1403.
  • Hiraiwa H, Pan CJ, Lin B, Akiyama TE, Gonzalez FJ, Chou JY. 2001. A molecular link between the common phenotypes of type 1 glycogen storage disease and HNF1alpha-null mice. J Biol Chem. 276(11):7963–7967.
  • Holton NW, Singhal M, Kumar A, Ticho AL, Manzella CR, Malhotra P, Jarava D, Saksena S, Dudeja PK, Alrefai WA, et al. 2020. Hepatocyte nuclear factor-4α regulates expression of the serotonin transporter in intestinal epithelial cells. Am J Physiol Cell Physiol. 318(6):C1294–C1304.
  • Hu M, Huang X, Han X, Ji L. 2020. Loss of HNF1α function contributes to hepatocyte proliferation and abnormal cholesterol metabolism via downregulating miR-122: a novel mechanism of MODY3. Diabetes Metab Syndr Obes. 13:627–639.
  • Hu DG, Marri S, Mckinnon RA, Mackenzie PI, Meech R. 2019. Deregulation of the genes that are involved in drug absorption, distribution, metabolism, and excretion in hepatocellular carcinoma. J Pharmacol Exp Ther. 368(3):363–381.
  • Hu DG, Meech R, Mckinnon RA, Mackenzie PI. 2014. Transcriptional regulation of human UDP-glucuronosyltransferase genes. Drug Metab Rev. 46(4):421–458.
  • Huck I, Gunewardena S, Espanol-Suner R, Willenbring H, Apte U. 2019. Hepatocyte nuclear factor 4 alpha activation is essential for termination of liver regeneration in mice. Hepatology. 70(2):666–681.
  • Hwang-Verslues WW, Sladek FM. 2010. HNF4α–role in drug metabolism and potential drug target? Curr Opin Pharmacol. 10(6):698–705.
  • Illés P, Krasulová K, Vyhlídalová B, Poulíková K, Marcalíková A, Pečinková P, Sirotová N, Vrzal R, Mani S, Dvořák Z. 2020. Indole microbial intestinal metabolites expand the repertoire of ligands and agonists of the human pregnane X receptor. Toxicol Lett. 334:87–93.
  • Ishii Y, Hansen AJ, Mackenzie PI. 2000. Octamer transcription factor-1 enhances hepatic nuclear factor-1alpha-mediated activation of the human UDP glucuronosyltransferase 2B7 promoter. Mol Pharmacol. 57(5):940–947.
  • Jin L, Kikuchi R, Saji T, Kusuhara H, Sugiyama Y. 2012. Regulation of tissue-specific expression of renal organic anion transporters by hepatocyte nuclear factor 1 α/β and DNA methylation. J Pharmacol Exp Ther. 340(3):648–655.
  • Jover R, Bort R, Gomez-Lechon MJ, Castell JV. 2001. Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: a study using adenovirus-mediated antisense targeting. Hepatology. 33(3):668–675.
  • Jover R, Moya M, Gomez-Lechon MJ. 2009. Transcriptional regulation of cytochrome p450 genes by the nuclear receptor hepatocyte nuclear factor 4-alpha. Curr Drug Metab. 10(5):508–519.
  • Jung D, Hagenbuch B, Gresh L, Pontoglio M, Meier PJ, Kullak-Ublick GA. 2001. Characterization of the human OATP-C (SLC21A6) gene promoter and regulation of liver-specific OATP genes by hepatocyte nuclear factor 1 alpha. J Biol Chem. 276(40):37206–37214.
  • Juřica J, Dovrtělová G, Nosková K, Zendulka O. 2016. Bile acids, nuclear receptors and cytochrome P450. Physiol Res. 65(Suppl 4):S427–S440.
  • Kajiwara M, Terada T, Asaka J, Aoki M, Katsura T, Ikai I, Inui K. 2008. Regulation of basal core promoter activity of human organic cation transporter 1 (OCT1/SLC22A1). Am J Physiol Gastrointest Liver Physiol. 295(6):G1211–G1216.
  • Kamiya A, Inoue Y, Gonzalez FJ. 2003. Role of the hepatocyte nuclear factor 4alpha in control of the pregnane X receptor during fetal liver development. Hepatology. 37(6):1375–1384.
  • Kamiyama Y, Matsubara T, Yoshinari K, Nagata K, Kamimura H, Yamazoe Y. 2007. Role of human hepatocyte nuclear factor 4α in the expression of drug-metabolizing enzymes and transporters in human hepatocytes assessed by use of small interfering RNA. Drug Metab Pharmacokinet. 22(4):287–298.
  • Kitao A, Matsui O, Yoneda N, Kozaka K, Kobayashi S, Koda W, Minami T, Inoue D, Yoshida K, Yamashita T, et al. 2018. Gadoxetic acid-enhanced magnetic resonance imaging reflects co-activation of β-catenin and hepatocyte nuclear factor 4α in hepatocellular carcinoma. Hepatol Res. 48(2):205–216.
  • Kleber ME, Grammer TB, Renner W, Marz W. 2010. Effect of the rs2259816 polymorphism in the HNF1A gene on circulating levels of c-reactive protein and coronary artery disease (the Ludwigshafen risk and cardiovascular health study). BMC Med Genet. 11:157.
  • Klein K, Winter S, Turpeinen M, Schwab M, Zanger UM. 2010. Pathway-Targeted pharmacogenomics of CYP1A2 in human liver. Front Pharmacol. 1(129):129.
  • Ko HL, Zhuo Z, Ren EC. 2019. HNF4α combinatorial isoform heterodimers activate distinct gene targets that differ from their corresponding homodimers. Cell Rep. 26(10):2549–2557.
  • Kong D, Xu H, Chen M, Yu Y, Qian Y, Qin T, Tong Y, Xia Q, Hang H. 2020. Co-encapsulation of HNF4α overexpressing UMSCs and human primary hepatocytes ameliorates mouse acute liver failure. Stem Cell Res Ther. 11(1):449.
  • Konstandi M, Cheng J, Gonzalez FJ. 2013. Sex steroid hormones regulate constitutive expression of Cyp2e1 in female mouse liver. Am J Physiol Endocrinol Metab. 304(10):E1118–E1128.
  • Lamba V, Ghodke Y, Guan W, Tracy TS. 2014. MicroRNA-34a is associated with expression of key hepatic transcription factors and cytochromes P450. Biochem Biophys Res Commun. 445(2):404–411.
  • Lambert É, Babeu J-P, Simoneau J, Raisch J, Lavergne L, Lévesque D, Jolibois É, Avino M, Scott MS, Boudreau F, et al. 2020. Human hepatocyte nuclear factor 4-α encodes isoforms with distinct transcriptional functions. Mol Cell Proteomics. 19(5):808–827.,.
  • Lau HH, Ng N, Loo L, Jasmen JB, Teo A. 2018. The molecular functions of hepatocyte nuclear factors – in and beyond the liver. J Hepatol. 68(5):1033–1048.
  • Lazarevich NL, Shavochkina DA, Fleishman DI, Kustova IF, Morozova OV, Chuchuev ES, Patyutko YI. 2010. Deregulation of hepatocyte nuclear factor 4 (HNF4) as a marker of epithelial tumors progression. Exp Oncol. 32(3):167–171.
  • Lee SH, Athavankar S, Cohen T, Piran R, Kiselyuk A, Levine F. 2013. Identification of alverine and benfluorex as HNF4α activators. ACS Chem Biol. 8(8):1730–1736.
  • Li Z, Chen H. 2019. MiR-34a inhibits proliferation, migration and invasion of paediatric neuroblastoma cells via targeting HNF4α. Artif Cells Nanomed Biotechnol. 47(1):3072–3078.
  • Li Y, Hao B, Muhammad I, Zhang Y, Yang Y, Shi C, Chang Y, Li R, Li C, Liu F. 2019. Acetaminophen-induced reduction in glutathione-S-transferase A1 in hepatocytes: a role for hepatic nuclear factor 1alpha and its response element. Biochem Biophys Res Commun. 516(1):251–257.
  • Li Y, Meng Q, Yang M, Liu D, Hou X, Tang L, Wang X, Lyu Y, Chen X, Liu K, et al. 2019. Current trends in drug metabolism and pharmacokinetics. Acta Pharm Sin B. 9(6):1113–1144.
  • Lim KT, Kim J, Hwang SI, Zhang L, Han H, Bae D, Kim KP, Hu YP, Scholer HR, Lee I, et al. 2018. Direct conversion of mouse fibroblasts into cholangiocyte progenitor cells. Stem Cell Reports. 10(5):1522–1536.
  • Lin J, Gu C, Shen Z, Liu Y, Wang W, Tao S, Cui X, Liu J, Xie Y. 2017. Hepatocyte nuclear factor 1α downregulates HBV gene expression and replication by activating the NF-κB signaling pathway. PLoS One. 12(3):e174017.
  • Liu SY, Gonzalez FJ. 1995. Role of the liver-enriched transcription factor HNF-1α in expression of the CYP2E1 gene. DNA Cell Biol. 14(4):285–293.
  • Lu H. 2016. Crosstalk of HNF4α with extracellular and intracellular signaling pathways in the regulation of hepatic metabolism of drugs and lipids. Acta Pharm Sin B. 6(5):393–408.
  • Lucas B, Grigo K, Erdmann S, Lausen J, Klein-Hitpass L, Ryffel GU. 2005. HNF4alpha reduces proliferation of kidney cells and affects genes deregulated in renal cell carcinoma. Oncogene. 24(42):6418–6431.
  • Lv DD, Zhou LY, Tang H. 2021. Hepatocyte nuclear factor 4α and cancer-related cell signaling pathways: a promising insight into cancer treatment. Exp Mol Med. 53(1):8–18.
  • Mackenzie PI, Hu DG, Gardner-Stephen DA. 2010. The regulation of UDP-glucuronosyltransferase genes by tissue-specific and ligand-activated transcription factors. Drug Metab Rev. 42(1):99–109.
  • Maestro MA, Cardalda C, Boj SF, Luco RF, Servitja JM, Ferrer J. 2007. Distinct roles of HNF1beta, HNF1alpha, and HNF4alpha in regulating pancreas development, beta-cell function and growth. Endocr Dev. 12:33–45.
  • Maher JM, Slitt AL, Callaghan TN, Cheng X, Cheung C, Gonzalez FJ, Klaassen CD. 2006. Alterations in transporter expression in liver, kidney, and duodenum after targeted disruption of the transcription factor HNF1alpha. Biochem Pharmacol. 72(4):512–522.
  • Martinez-Jimenez CP, Castell JV, Gomez-Lechon MJ, Jover R. 2006. Transcriptional activation of CYP2C9, CYP1A1, and CYP1A2 by hepatocyte nuclear factor 4α requires coactivators peroxisomal proliferator activated receptor-γ coactivator 1α and steroid receptor coactivator 1. Mol Pharmacol. 70(5):1681–1692.
  • Matsumura K, Saito T, Takahashi Y, Ozeki T, Kiyotani K, Fujieda M, Yamazaki H, Kunitoh H, Kamataki T. 2004. Identification of a novel polymorphic enhancer of the human CYP3A4 gene. Mol Pharmacol. 65(2):326–334.
  • Meijer I, Willems S, Ni X, Heering J, Chaikuad A, Merk D. 2020. Chemical starting matter for HNF4α ligand discovery and chemogenomics. IJMS. 21(21):7895.
  • Moulin P, Andre M, Alawi H, Dos SL, Khalid AK, Koev D, Moore R, Serban V, Picandet B, Francillard M. 2006. Efficacy of benfluorex in combination with sulfonylurea in type 2 diabetic patients: an 18-week, randomized, double-blind study. Diabetes Care. 29(3):515–520.
  • Mounajjed T, Yasir S, Aleff PA, Torbenson MS. 2015. Pigmented hepatocellular adenomas have a high risk of atypia and malignancy. Mod Pathol. 28(9):1265–1274.
  • Mubarokah N, Hulin JA, Mackenzie PI, Mckinnon RA, Haines AZ, Hu DG, Meech R. 2018. Cooperative regulation of intestinal UDP-glucuronosyltransferases 1A8, -1A9, and 1A10 by CDX2 and HNF4α is mediated by a novel composite regulatory element. Mol Pharmacol. 93(5):541–552.
  • Ni Q, Ding K, Wang KQ, He J, Yin C, Shi J, Zhang X, Xie WF, Shi YQ. 2017. Deletion of HNF1α in hepatocytes results in fatty liver-related hepatocellular carcinoma in mice. FEBS Lett. 591(13):1947–1957.
  • Ning BF, Ding J, Yin C, Zhong W, Wu K, Zeng X, Yang W, Chen YX, Zhang JP, Zhang X, et al. 2010. Hepatocyte nuclear factor 4 alpha suppresses the development of hepatocellular carcinoma. Cancer Res. 70(19):7640–7651.
  • Nozaki K, Nakano M, Iwakami C, Fukami T, Nakajima M. 2019. RNA editing enzymes modulate the expression of hepatic CYP2B6, CYP2C8, and other cytochrome p450 isoforms. Drug Metab Dispos. 47(6):639–647.
  • Nuclear Receptors Nomenclature Committee. 1999. A unified nomenclature system for the nuclear receptor superfamily. Cell. 97(2):161–163.
  • Odom DT, Zizlsperger N, Gordon DB, Bell GW, Rinaldi NJ, Murray HL, Volkert TL, Schreiber J, Rolfe PA, Gifford DK, et al. 2004. Control of pancreas and liver gene expression by HNF transcription factors. Science. 303(5662):1378–1381.
  • Ondo K, Isono M, Nakano M, Hashiba S, Fukami T, Nakajima M. 2021. The N6-methyladenosine modification posttranscriptionally regulates hepatic UGT2B7 expression. Biochem Pharmacol. 189:114402.
  • Park SH, Waxman DJ. 2001. Inhibitory cross-talk between STAT5b and liver nuclear factor HNF3beta: Impact on the regulation of growth hormone pulse-stimulated, male-specific liver cytochrome P-450 gene expression. J Biol Chem. 276(46):43031–43039.
  • Patitucci C, Couchy G, Bagattin A, Caneque T, de Reynies A, Scoazec JY, Rodriguez R, Pontoglio M, Zucman-Rossi J, Pende M, et al. 2017. Hepatocyte nuclear factor 1α suppresses steatosis-associated liver cancer by inhibiting PPARγ transcription. J Clin Invest. 127(5):1873–1888.
  • Pearson ER, Boj SF, Steele AM, Barrett T, Stals K, Shield JP, Ellard S, Ferrer J, Hattersley AT. 2007. Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene. PLoS Med. 4(4):e118.
  • Pearson ER, Starkey BJ, Powell RJ, Gribble FM, Clark PM, Hattersley AT. 2003. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet. 362(9392):1275–1281.
  • Piessen G, Jonckheere N, Vincent A, Hemon B, Ducourouble MP, Copin MC, Mariette C, Van Seuningen I. 2007. Regulation of the human mucin MUC4 by taurodeoxycholic and taurochenodeoxycholic bile acids in oesophageal cancer cells is mediated by hepatocyte nuclear factor 1alpha. Biochem J. 402(1):81–91.
  • Prajapati KD, Sharma SS, Roy N. 2012. Hepatocyte nuclear factor-1alpha mediated upregulation of albumin expression in focal ischemic rat brain. Neurol Res. 34(1):25–31.
  • Prie D. 2014. Familial renal glycosuria and modifications of glucose renal excretion. Diabetes Metab. 40(6 Suppl 1):S12–S16.
  • Qadri I, Hu LJ, Iwahashi M, Al-Zuabi S, Quattrochi LC, Simon FR. 2009. Interaction of hepatocyte nuclear factors in transcriptional regulation of tissue specific hormonal expression of human multidrug resistance-associated protein 2 (abcc2). Toxicol Appl Pharmacol. 234(3):281–292.
  • Qadri I, Iwahashi M, Kullak-Ublick GA, Simon FR. 2006. Hepatocyte nuclear factor (HNF) 1 and HNF4 mediate hepatic multidrug resistance protein 2 up-regulation during hepatitis C virus gene expression. Mol Pharmacol. 70(2):627–636.
  • Qian H, Deng X, Huang ZW, Wei J, Ding CH, Feng RX, Zeng X, Chen YX, Ding J, Qiu L, et al. 2015. An HNF1α-regulated feedback circuit modulates hepatic fibrogenesis via the crosstalk between hepatocytes and hepatic stellate cells. Cell Res. 25(8):930–945.
  • Ramirez J, Mirkov S, Zhang W, Chen P, Das S, Liu W, Ratain MJ, Innocenti F. 2008. Hepatocyte nuclear factor-1 alpha is associated with UGT1A1, UGT1A9 and UGT2B7 mRNA expression in human liver. Pharmacogenomics J. 8(2):152–161.
  • Rana R, Chen Y, Ferguson SS, Kissling GE, Surapureddi S, Goldstein JA. 2010. Hepatocyte nuclear factor 4{alpha} regulates rifampicin-mediated induction of CYP2C genes in primary cultures of human hepatocytes. Drug Metab Dispos. 38(4):591–599.
  • Rebouissou S, Bioulac-Sage P, Zucman-Rossi J. 2008. Molecular pathogenesis of focal nodular hyperplasia and hepatocellular adenoma. J Hepatol. 48(1):163–170.
  • Rebouissou S, Vasiliu V, Thomas C, Bellanne-Chantelot C, Bui H, Chretien Y, Timsit J, Rosty C, Laurent-Puig P, Chauveau D, et al. 2005. Germline hepatocyte nuclear factor 1alpha and 1beta mutations in renal cell carcinomas. Hum Mol Genet. 14(5):603–614.
  • Rosenthal SB, Bush KT, Nigam SK. 2019. A network of SLC and ABC transporter and DME genes involved in remote sensing and signaling in the gut-liver-kidney axis. Sci Rep. 9(1):11879.
  • Rosner GL, Panetta JC, Innocenti F, Ratain MJ. 2008. Pharmacogenetic pathway analysis of irinotecan. Clin Pharmacol Ther. 84(3):393–402.
  • Saha SK, Parachoniak CA, Ghanta KS, Fitamant J, Ross KN, Najem MS, Gurumurthy S, Akbay EA, Sia D, Cornella H, et al. 2014. Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer. Nature. 513(7516):110–114.
  • Sato Y, Rahman MM, Haneda M, Tsuyama T, Mizumoto T, Yoshizawa T, Kitamura T, Gonzalez FJ, Yamamura K, Yamagata K. 2020. HNF1α controls glucagon secretion in pancreatic α-cells through modulation of SGLT1. Biochim Biophys Acta Mol Basis Dis. 1866(11):165898.
  • Servitja JM, Pignatelli M, Maestro MA, Cardalda C, Boj SF, Lozano J, Blanco E, Lafuente A, Mccarthy MI, Sumoy L, et al. 2009. Hnf1α (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver. Mol Cell Biol. 29(11):2945–2959.
  • Shen CH, Zhang YX, Lu RY, Jin B, Wang S, Liu ZR, Tang YL, Ding MP. 2016. Specific OCT1 and ABCG2 polymorphisms are associated with lamotrigine concentrations in Chinese patients with epilepsy. Epilepsy Res. 127:186–190.
  • Shih DQ, Bussen M, Sehayek E, Ananthanarayanan M, Shneider BL, Suchy FJ, Shefer S, Bollileni JS, Gonzalez FJ, Breslow JL, et al. 2001. Hepatocyte nuclear factor-1α is an essential regulator of bile acid and plasma cholesterol metabolism. Nat Genet. 27(4):375–382.
  • Skowronek R, Czekaj P, Suszka-Świtek A, Czech E, Wiaderkiewicz A, Plewka D, Bryzek A. 2016. Expression of cytochrome P450 2C and 3A in female rat liver after long-term administration of gonadoliberin analogs. Int J Occup Med Environ Health. 29(2):293–314.
  • Spaninger E, Potocnik U, Bren U. 2020. Molecular dynamics simulations predict that rSNP located in the HNF1α gene promotor region linked with MODY3 and hepatocellular carcinoma promotes stronger binding of the HNF4α transcription factor. Biomolecules. 10(12):1700.
  • Stoffel M, Duncan SA. 1997. The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci USA. 94(24):13209–13214.
  • Subramani R, Medel J, Flores K, Perry C, Galvez A, Sandoval M, Rivera S, Pedroza DA, Penner E, Chitti M, et al. 2020. Hepatocyte nuclear factor 1 alpha influences pancreatic cancer growth and metastasis. Sci Rep. 10(1):20225.
  • Sucajtys-Szulc E, Debska-Slizien A, Rutkowski B, Milczarek R, Pelikant-Malecka I, Sledzinski T, Swierczynski J, Szolkiewicz M. 2018. Hepatocyte nuclear factors as possible C-reactive protein transcriptional inducer in the liver and white adipose tissue of rats with experimental chronic renal failure. Mol Cell Biochem. 446(1–2):11–23.
  • Sugai M, Umezu H, Yamamoto T, Jiang S, Iwanari H, Tanaka T, Hamakubo T, Kodama T, Naito M. 2008. Expression of hepatocyte nuclear factor 4 alpha in primary ovarian mucinous tumors. Pathol Int. 58(11):681–686.
  • Sugano M, Nagasaka T, Sasaki E, Murakami Y, Hosoda W, Hida T, Mitsudomi T, Yatabe Y. 2013. HNF4α as a marker for invasive mucinous adenocarcinoma of the lung. Am J Surg Pathol. 37(2):211–218.
  • Sugatani J, Wada T, Osabe M, Yamakawa K, Yoshinari K, Miwa M. 2006. Dietary inulin alleviates hepatic steatosis and xenobiotics-induced liver injury in rats fed a high-fat and high-sucrose diet: association with the suppression of hepatic cytochrome P450 and hepatocyte nuclear factor 4alpha expression. Drug Metab Dispos. 34(10):1677–1687.
  • Sugawara M, Okamoto K, Kadowaki T, Kusano K, Fukamizu A, Yoshimura T. 2010. Expressions of cytochrome P450, UDP-glucuronosyltranferase, and transporter genes in monolayer carcinoma cells change in subcutaneous tumors grown as xenografts in immunodeficient nude mice. Drug Metab Dispos. 38(3):526–533.
  • Sun Q, Xu W, Ji S, Qin Y, Liu W, Hu Q, Zhang Z, Liu M, Yu X, Xu X. 2019. Role of hepatocyte nuclear factor 4 alpha in cell proliferation and gemcitabine resistance in pancreatic adenocarcinoma. Cancer Cell Int. 19:49.
  • Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. 2007. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131(5):861–872.
  • Tan J, Xu J, Wei G, Zhang L, Sun L, Wang G, Li F, Jiang F. 2019. HNF1α controls liver lipid metabolism and insulin resistance via negatively regulating the SOCS-3-STAT3 signaling pathway. J Diabetes Res. 2019:5483946.
  • Tanaka Y, Chen C, Maher JM, Klaassen CD. 2006. Kupffer cell-mediated downregulation of hepatic transporter expression in rat hepatic ischemia-reperfusion. Transplantation. 82(2):258–266.
  • Tanaka T, Jiang S, Hotta H, Takano K, Iwanari H, Sumi K, Daigo K, Ohashi R, Sugai M, Ikegame C, et al. 2006. Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer. J Pathol. 208(5):662–672.
  • Taneja G, Maity S, Jiang W, Moorthy B, Coarfa C, Ghose R. 2019. Transcriptomic profiling identifies novel mechanisms of transcriptional regulation of the cytochrome P450 (Cyp)3a11 gene. Sci Rep. 9(1):6663.
  • Tavares-Sanchez OL, Rodriguez C, Gortares-Moroyoqui P, Estrada MI. 2015. Hepatocyte nuclear factor-4α, a multifunctional nuclear receptor associated with cardiovascular disease and cholesterol catabolism. Int J Environ Health Res. 25(2):126–139.
  • Teeli AS, Łuczyńska K, Haque E, Gayas MA, Winiarczyk D, Taniguchi H. 2021. Disruption of tumor suppressors HNF4α/HNF1α causes tumorigenesis in liver. Cancers. 13(21):5357.
  • Terryn S, Tanaka K, Lengele JP, Olinger E, Dubois-Laforgue D, Garbay S, Kozyraki R, Van Der Smissen P, Christensen EI, Courtoy PJ, et al. 2016. Tubular proteinuria in patients with HNF1α mutations: HNF1α drives endocytosis in the proximal tubule. Kidney Int. 89(5):1075–1089.
  • Thangavel C, Boopathi E, Shapiro BH. 2013. Inherent sex-dependent regulation of human hepatic CYP3A5. Br J Pharmacol. 168(4):988–1000.
  • Thomas C, Landrier JF, Gaillard D, Grober J, Monnot MC, Athias A, Besnard P. 2006. Cholesterol dependent downregulation of mouse and human apical sodium dependent bile acid transporter (ASBT) gene expression: molecular mechanism and physiological consequences. Gut. 55(9):1321–1331.
  • Tirona RG, Kim RB. 2005. Nuclear receptors and drug disposition gene regulation. J Pharm Sci. 94(6):1169–1186.
  • Tirona RG, Lee W, Leake BF, Lan LB, Cline CB, Lamba V, Parviz F, Duncan SA, Inoue Y, Gonzalez FJ, et al. 2003. The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4. Nat Med. 9(2):220–224.
  • Torres-Padilla ME, Fougere-Deschatrette C, Weiss MC. 2001. Expression of HNF4alpha isoforms in mouse liver development is regulated by sequential promoter usage and constitutive 3' end splicing. Mech Dev. 109(2):183–193.
  • Uno Y, Sakamoto Y, Yoshida K, Hasegawa T, Hasegawa Y, Koshino T, Inoue I. 2003. Characterization of six base pair deletion in the putative HNF1-binding site of human PXR promoter. J Hum Genet. 48(11):594–597.
  • van der Post RS, Bult P, Vogelaar IP, Ligtenberg MJ, Hoogerbrugge N, van Krieken JH. 2014. HNF4A immunohistochemistry facilitates distinction between primary and metastatic breast and gastric carcinoma. Virchows Arch. 464(6):673–679.
  • Velenosi TJ, Feere DA, Sohi G, Hardy DB, Urquhart BL. 2014. Decreased nuclear receptor activity and epigenetic modulation associates with down-regulation of hepatic drug-metabolizing enzymes in chronic kidney disease. FASEB J. 28(12):5388–5397.
  • Vuong LM, Chellappa K, Dhahbi JM, Deans JR, Fang B, Bolotin E, Titova NV, Hoverter NP, Spindler SR, Waterman ML, et al. 2015. Differential effects of hepatocyte nuclear factor 4α isoforms on tumor growth and T-Cell factor 4/AP-1 interactions in human colorectal cancer cells. Mol Cell Biol. 35(20):3471–3490.
  • Walesky C, Apte U. 2015. Role of hepatocyte nuclear factor 4α (HNF4α) in cell proliferation and cancer. Gene Expr. 16(3):101–108.
  • Wang P, Chen S, Wang Y, Wang X, Yan L, Yang K, Zhong XB, Han S, Zhang L. 2021. The long noncoding RNA hepatocyte nuclear factor 4α antisense RNA 1 negatively regulates cytochrome P450 enzymes in Huh7 cells via histone modifications. Drug Metab Dispos. 49(5):361–368.
  • Wang X, Hassan W, Zhao J, Bakht S, Nie Y, Wang Y, Pang Q, Huang Z. 2019. The impact of hepatocyte nuclear factor-1α on liver malignancies and cell stemness with metabolic consequences. Stem Cell Res Ther. 10(1):315.
  • Wang Z, Li Y, Wu D, Yu S, Wang Y, Leung CF. 2020. Nuclear receptor HNF4α performs a tumor suppressor function in prostate cancer via its induction of p21-driven cellular senescence. Oncogene. 39(7):1572–1589.
  • Wang AW, Wang YJ, Zahm AM, Morgan AR, Wangensteen KJ, Kaestner KH. 2020. The dynamic chromatin architecture of the regenerating liver. Cell Mol Gastroenterol Hepatol. 9(1):121–143.
  • Wang Y, Yan L, Liu J, Chen S, Liu G, Nie Y, Wang P, Yang W, Chen L, Zhong X, et al. 2019. The HNF1α-regulated lncRNA HNF1α-AS1 is involved in the regulation of cytochrome p450 expression in human liver tissues and huh7 cells. J Pharmacol Exp Ther. 368(3):353–362.
  • Wang Z, Zhang Y, Zhang J, Deng Q, Liang H. 2021. Controversial roles of hepatocyte nuclear receptor 4α on tumorigenesis. Oncol Lett. 21(5):356.
  • Wells PG, Mackenzie PI, Chowdhury JR, Guillemette C, Gregory PA, Ishii Y, Hansen AJ, Kessler FK, Kim PM, Chowdhury NR, et al. 2004. Glucuronidation and the UDP-glucuronosyltransferases in health and disease. Drug Metab Dispos. 32(3):281–290.
  • Wiwi CA, Waxman DJ. 2004. Role of hepatocyte nuclear factors in growth hormone-regulated, sexually dimorphic expression of liver cytochromes P450. Growth Factors. 22(2):79–88.
  • Wortham M, Czerwinski M, He L, Parkinson A, Wan YJ. 2007. Expression of constitutive androstane receptor, hepatic nuclear factor 4 alpha, and P450 oxidoreductase genes determines interindividual variability in basal expression and activity of a broad scope of xenobiotic metabolism genes in the human liver. Drug Metab Dispos. 35(9):1700–1710.
  • Wu M, Dong B, Cao A, Li H, Liu J. 2012. Delineation of molecular pathways that regulate hepatic PCSK9 and LDL receptor expression during fasting in normolipidemic hamsters. Atherosclerosis. 224(2):401–410.
  • Xie HG, Lee W, Yu C, Stein CM, Kim RB. 2005. Hepatocyte nuclear factors (HNF) 4α and 1α synergistically up-regulate car-mediated transcriptional activity of human CYP2C9 gene. Clin Pharmacol Ther. 77(2):P23–P23.
  • Xu J, Filetti S, Hershman JM. 2008. Expression of hepatocyte nuclear factor-1alpha mRNA in human anaplastic thyroid cancer cell lines and tumors. Thyroid. 18(5):533–539.
  • Xu Q, Li Y, Gao X, Kang K, Williams JG, Tong L, Liu J, Ji M, Deterding LJ, Tong X, et al. 2020. HNF4α regulates sulfur amino acid metabolism and confers sensitivity to methionine restriction in liver cancer. Nat Commun. 11(1):3978.
  • Xu C, Ooi WF, Qamra A, Tan J, Chua BY, Ho SWT, Das K, Adam Isa ZF, Li Z, Yao X, et al. 2020. HNF4α pathway mapping identifies wild-type IDH1 as a targetable metabolic node in gastric cancer. Gut. 69(2):231–242.
  • Xu Y, Zhu Y, Hu S, Xu Y, Stroup D, Pan X, Bawa FC, Chen S, Gopoju R, Yin L, et al. 2021. Hepatocyte nuclear factor 4α prevents the steatosis-to-NASH progression by regulating p53 and bile acid signaling (in mice). Hepatology. 73(6):2251–2265.
  • Yamagata K. 2014. Roles of HNF1alpha and HNF4alpha in pancreatic beta-cells: lessons from a monogenic form of diabetes (MODY). Vitam Horm. 95:407–423.
  • Yamagata K, Furuta H, Oda N, Kaisaki PJ, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M, Bell GI. 1996. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature. 384(6608):458–460.
  • Yamagata K, Oda N, Kaisaki PJ, Menzel S, Furuta H, Vaxillaire M, Southam L, Cox RD, Lathrop GM, Boriraj VV, et al. 1996. Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3). Nature. 384(6608):455–458.
  • Yang G, Zhang M, Zhao Y, Pan Y, Kan M, Li J, He K, Zhang X. 2020. HNF-4α inhibits hepatocellular carcinoma cell proliferation through mir-122-adam17 pathway. PLoS One. 15(3):e230450.
  • Yeh MM, Bosch DE, Daoud SS. 2019. Role of hepatocyte nuclear factor 4-alpha in gastrointestinal and liver diseases. World J Gastroenterol. 25(30):4074–4091.
  • Yuan X, Lu H, Zhao A, Ding Y, Min Q, Wang R. 2020. Transcriptional regulation of CYP3A4 by nuclear receptors in human hepatocytes under hypoxia. Drug Metab Rev. 52(2):225–234.
  • Yue HY, Yin C, Hou JL, Zeng X, Chen YX, Zhong W, Hu PF, Deng X, Tan YX, Zhang JP, et al. 2010. Hepatocyte nuclear factor 4α attenuates hepatic fibrosis in rats. Gut. 59(2):236–246.
  • Yueh MF, Mellon PL, Tukey RH. 2011. Inhibition of human UGT2B7 gene expression in transgenic mice by the constitutive androstane receptor. Mol Pharmacol. 79(6):1053–1060.
  • Zeng X, Lin Y, Yin C, Zhang X, Ning BF, Zhang Q, Zhang JP, Qiu L, Qin XR, Chen YX, et al. 2011. Recombinant adenovirus carrying the hepatocyte nuclear factor-1alpha gene inhibits hepatocellular carcinoma xenograft growth in mice. Hepatology. 54(6):2036–2047.
  • Zhang Y, Li R, Rong W, Han M, Cui C, Feng Z, Sun X, Jin S. 2018. Therapeutic effect of hepatocyte growth factor-overexpressing bone marrow-derived mesenchymal stem cells on CCl4-induced hepatocirrhosis. Cell Death Dis. 9(12):1186.
  • Zhang L, Xu P, Cheng Y, Wang P, Ma X, Liu M, Wang X, Xu F. 2019. Diet-induced obese alters the expression and function of hepatic drug-metabolizing enzymes and transporters in rats. Biochem Pharmacol. 164:368–376.
  • Zhou Y, Wang X, Li H, Zhang J, Chen Z, Xie W, Zhang J, Li J, Zhou L, Huang M. 2015. Polymorphisms of ABCG2, ABCB1 and HNF4α are associated with Lamotrigine trough concentrations in epilepsy patients. Drug Metab Pharmacokinet. 30(4):282–287.
  • Zhou YJ, Yin RX, Hong SC, Yang Q, Cao XL, Chen WX. 2017. Association of the HNF1A polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke. J Gene Med. 19(1–2):e2941.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.