Crosstalk of HNF4α with extracellular and intracellular signaling pathways in the regulation of hepatic metabolism of drugs and lipids

Acta Pharmaceutica Sinica B

Volumn 6, Issue 5, 2016, Pages 393-408

  Lu, Hong ^a  

^a State University of New York Upstate Medical University: College of Medicine   (United States)

Author keywords

Drug metabolism; HNF4 ; Hormone; Inflammation; Lipid metabolism; Liver

Indexed keywords

BETA CATENIN; CARBOXYLYASE; CHICKEN OVALBUMIN UPSTREAM PROMOTER TRANSCRIPTION FACTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; CYCLIN D1; ESTROGEN RECEPTOR ALPHA; FARNESOID X RECEPTOR; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; GLUCOSE 6 PHOSPHATASE; GROWTH HORMONE; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; HES FAMILY BHLH TRANSCRIPTION FACTOR 6; JANUS KINASE 2; KRUPPEL LIKE FACTOR 9; MYC PROTEIN; ORPHAN NUCLEAR RECEPTOR; ORPHAN NUCLEAR RECEPTOR SHP; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PHOENOLPYRUVATE CARBOXYKINASE; PREGNANE X RECEPTOR; PROTEIN P53; SATURATED FATTY ACID; SMAD PROTEIN; STAT5 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR SP1; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UNINDEXED DRUG; UNSATURATED FATTY ACID;

CELL DEATH; DOWN REGULATION; DRUG METABOLISM; EXTRACELLULAR SIGNALING PATHWAY; GENE EXPRESSION; HUMAN; INFLAMMATION; INTRACELLULAR SIGNALING; LIPID METABOLISM; LIVER; MUTATION; NONHUMAN; PROTEIN ACETYLATION; PROTEIN EXPRESSION; PROTEIN METHYLATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION; TRANSACTIVATION; TRANSLATION REGULATION;

EID: 84995332343     PISSN: 22113835     EISSN: 22113843     Source Type: Journal    
DOI: 10.1016/j.apsb.2016.07.003     Document Type: Review

References (214)

1. 1 Li, J.X., Ning, G., Duncan, S.A., Mammalian hepatocyte differentiation requires the transcription factor HNF-4α. Genes Dev 14 (2000), 464-474.
2. 2 Kyrmizi, I., Hatzis, P., Katrakili, N., Tronche, F., Gonzalez, F.J., Talianidis, I., Plasticity and expanding complexity of the hepatic transcription factor network during liver development. Genes Dev 20 (2006), 2293-2305.
3. 3 Hayhurst, G.P., Lee, Y.H., Lambert, G., Ward, J.M., Gonzalez, F.J., Hepatocyte nuclear factor 4α (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol 21 (2001), 1393-1403.
4. 4 Gonzalez, F.J., Regulation of hepatocyte nuclear factor 4α-mediated transcription. Drug Metab Pharmacokinet 23 (2008), 2-7.
5. 5 Hwang-Verslues, W.W., Sladek, F.M., HNF4α—role in drug metabolism and potential drug target?. Curr Opin Pharmacol 10 (2010), 698-705.
6. 6 Bonzo, J.A., Ferry, C.H., Matsubara, T., Kim, J.H., Gonzalez, F.J., Suppression of hepatocyte proliferation by hepatocyte nuclear factor 4α in adult mice. J Biol Chem 287 (2012), 7345-7356.
7. 7 Inoue, Y., Hayhurst, G.P., Inoue, J., Mori, M., Gonzalez, F.J., Defective ureagenesis in mice carrying a liver-specific disruption of hepatocyte nuclear factor 4α (HNF4α). HNF4α regulates ornithine transcarbamylase in vivo. J Biol Chem 277 (2002), 25257-25265.
8. 8 Inoue, Y., Yu, A.M., Inoue, J., Gonzalez, F.J., Hepatocyte nuclear factor 4α is a central regulator of bile acid conjugation. J Biol Chem 279 (2004), 2480-2489.
9. 9 Inoue, Y., Yu, A.M., Yim, S.H., Ma, X.C., Krausz, K.W., Inoue, J., et al. Regulation of bile acid biosynthesis by hepatocyte nuclear factor 4α. J Lipid Res 47 (2006), 215-227.
10. 10 Lu, H., Gonzalez, F.J., Klaassen, C., Alterations in hepatic mRNA expression of phase II enzymes and xenobiotic transporters after targeted disruption of hepatocyte nuclear factor 4 alpha. Toxicol Sci 118 (2010), 380-390.
11. 11 Holloway, M.G., Miles, G.D., Dombkowski, A.A., Waxman, D.J., Liver-specific hepatocyte nuclear factor-4α deficiency: greater impact on gene expression in male than in female mouse liver. Mol Endocrinol 22 (2008), 1274-1286.
12. 12 Zhou, Z.X., Kang, X.Q., Jiang, Y.C., Song, Z.Y., Feng, W.K., McClain, C.J., et al. Preservation of hepatocyte nuclear factor-4α is associated with zinc protection against TNF-α hepatotoxicity in mice. Exp Biol Med 232 (2007), 622-628.
13. 13 Lazarevich, N.L., Cheremnova, O.A., Varga, E.V., Ovchinnikov, D.A., Kudrjavtseva, E.I., Morozova, O.V., et al. Progression of HCC in mice is associated with a downregulation in the expression of hepatocyte nuclear factors. Hepatology 39 (2004), 1038-1047.
14. 14 Berasain, C., Herrero, J.I., García-Trevijano, E.R., Avila, M.A., Esteban, J.I., Mato, J.M., et al. Expression of Wilms׳ tumor suppressor in the liver with cirrhosis: relation to hepatocyte nuclear factor 4 and hepatocellular function. Hepatology 38 (2003), 148-157.
15. 15 Kang, X.Q., Zhong, W., Liu, J., Song, Z.Y., McClain, C.J., Kang, Y.J., et al. Zinc supplementation reverses alcohol-induced steatosis in mice through reactivating hepatocyte nuclear factor-4α and peroxisome proliferator-activated receptor-α. Hepatology 50 (2009), 1241-1250.
16. 16 Xu, Y., Zalzala, M., Xu, J.S., Li, Y.Y., Yin, L.Y., Zhang, Y.Q., A metabolic stress-inducible miR-34a-HNF4α pathway regulates lipid and lipoprotein metabolism. Nat Commun, 6, 2015, 7466.
17. 17 Sekiya, S., Suzuki, A., Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors. Nature 475 (2011), 390-393.
18. 18 Ning, B.F., Ding, J., Yin, C., Zhong, W., Wu, K., Zeng, X., et al. Hepatocyte nuclear factor 4α suppresses the development of hepatocellular carcinoma. Cancer Res 70 (2010), 7640-7651.
19. 19 Yue, H.Y., Yin, C., Hou, J.L., Zeng, X., Chen, Y.X., Zhong, W., et al. Hepatocyte nuclear factor 4α attenuates hepatic fibrosis in rats. Gut 59 (2010), 236-246.
20. 20 Yin, C., Lin, Y., Zhang, X., Chen, Y.X., Zeng, X., Yue, H.Y., et al. Differentiation therapy of hepatocellular carcinoma in mice with recombinant adenovirus carrying hepatocyte nuclear factor-4α gene. Hepatology 48 (2008), 1528-1539.
21. 21 Hertz, R., Magenheim, J., Berman, I., Bar-Tana, J., Fatty acyl-CoA thioesters are ligands of hepatic nuclear factor-4α. Nature 392 (1998), 512-516.
22. 22 Walesky, C., Apte, U., Role of hepatocyte nuclear factor 4α (HNF4α) in cell proliferation and cancer. Gene Expr 16 (2015), 101-108.
23. 23 Babeu, J.P., Boudreau, F., Hepatocyte nuclear factor 4-alpha involvement in liver and intestinal inflammatory networks. World J Gastroenterol 20 (2014), 22-30.
24. 24 Chiang, J.Y., Hepatocyte nuclear factor 4α regulation of bile acid and drug metabolism. Expert Opin Drug Metab Toxicol 5 (2009), 137-147.
25. 25 Lazarevich, N.L., Shavochkina, D.A., Fleishman, D.I., Kustova, I.F., Morozova, O.V., Chuchuev, E.S., et al. Deregulation of hepatocyte nuclear factor 4 (HNF4) as a marker of epithelial tumors progression. Exp Oncol 32 (2010), 167-171.
26. 26 Niehof, M., Borlak, J., EPS15R, TASP1, and PRPF3 are novel disease candidate genes targeted by HNF4α splice variants in hepatocellular carcinomas. Gastroenterology 134 (2008), 1191-1202.
27. 27 Briançon, N., Bailly, A., Clotman, F., Jacquemin, P., Lemaigre, F.P., Weiss, M.C., Expression of the α7 isoform of hepatocyte nuclear factor (HNF) 4 is activated by HNF6/OC-2 and HNF1 and repressed by HNF4α1 in the liver. J Biol Chem 279 (2004), 33398-33408.
28. 28 Torres-Padilla, M.E., Sladek, F.M., Weiss, M.C., Developmentally regulated N-terminal variants of the nuclear receptor hepatocyte nuclear factor 4α mediate multiple interactions through coactivator and corepressor-histone deacetylase complexes. J Biol Chem 277 (2002), 44677-44687.
29. 29 Briançon, N., Weiss, M.C., In vivo role of the HNF4α AF-1 activation domain revealed by exon swapping. EMBO J 25 (2006), 1253-1262.
30. 30 Iyemere, V.P., Davies, N.H., Brownlee, G.G., The activation function 2 domain of hepatic nuclear factor 4 is regulated by a short C-terminal proline-rich repressor domain. Nucleic Acids Res 26 (1998), 2098-2104.
31. 31 Chandra, V., Huang, P.X., Potluri, N., Wu, D.L., Kim, Y., Rastinejad, F., Multidomain integration in the structure of the HNF-4α nuclear receptor complex. Nature 495 (2013), 394-398.
32. 32 Vuong, L.M., Chellappa, K., Dhahbi, J.M., Deans, J.R., Fang, B., Bolotin, E., et al. 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 (2015), 3471-3490.
33. 33 Thomas, A.M., Hart, S.N., Li, G.D., Lu, H., Fang, Y.P., Fang, J.W., et al. Hepatocyte nuclear factor 4 alpha and farnesoid X receptor co-regulates gene transcription in mouse livers on a genome-wide scale. Pharm Res 30 (2013), 2188-2198.
34. 34 Bolotin, E., Liao, H.L., Ta, T.C., Yang, C.H., Hwang-Verslues, W., Evans, J.R., et al. Integrated approach for the identification of human hepatocyte nuclear factor 4α target genes using protein binding microarrays. Hepatology 51 (2010), 642-653.
35. 35 Cicchini, C., de Nonno, V., Battistelli, C., Cozzolino, A.M., De Santis Puzzonia, M., Ciafrè, S.A., et al. Epigenetic control of EMT/MET dynamics: HNF4α impacts DNMT3s through miRs-29. Biochim Biophys Acta 1849 (2015), 919-929.
36. 36 Zhang, Q.H., Lei, X.H., Lu, H., Alterations of epigenetic signatures in hepatocyte nuclear factor 4α deficient mouse liver determined by improved ChIP-qPCR and (h)MeDIP-qPCR assays. PLoS One, 9, 2014, e84925.
37. 37 Jiang, G.Q., Sladek, F.M., The DNA binding domain of hepatocyte nuclear factor 4 mediates cooperative, specific binding to DNA and heterodimerization with the retinoid X receptor α. J Biol Chem 272 (1997), 1218-1225.
38. 38 Dhe-Paganon, S., Duda, K., Iwamoto, M., Chi, Y.I., Shoelson, S.E., Crystal structure of the HNF4α ligand binding domain in complex with endogenous fatty acid ligand. J Biol Chem 277 (2002), 37973-37976.
39. 39 Yuan, X.H., Ta, T.C., Lin, M., Evans, J.R., Dong, Y.C., Bolotin, E., et al. Identification of an endogenous ligand bound to a native orphan nuclear receptor. PLoS One, 4, 2009, e5609.
40. 40 Hertz, R., Kalderon, B., Byk, T., Berman, I., Za׳tara, G., Mayer, R., et al. Thioesterase activity and acyl-CoA/fatty acid cross-talk of hepatocyte nuclear factor-4α. J Biol Chem 280 (2005), 24451-24461.
41. 41 McIntosh, A.L., Petrescu, A.D., Hostetler, H.A., Kier, A.B., Schroeder, F., Liver-type fatty acid binding protein interacts with hepatocyte nuclear factor 4α. FEBS Lett 587 (2013), 3787-3791.
42. 42 Barrero, M.J., Malik, S., Two functional modes of a nuclear receptor-recruited arginine methyltransferase in transcriptional activation. Mol Cell 24 (2006), 233-243.
43. 43 Hornbeck, P.V., Zhang, B., Murray, B., Kornhauser, J.M., Latham, V., Skrzypek E. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res, 43, 2015 D512-20.
44. 44 Soutoglou, E., Katrakili, N., Talianidis, I., Acetylation regulates transcription factor activity at multiple levels. Mol Cell 5 (2000), 745-751.
45. 45 Guo, H.T., Gao, C.J., Mi, Z.Y., Zhang, J.P., Kuo, P.C., Characterization of the PC4 binding domain and its interactions with HNF4α. J Biochem 141 (2007), 635-640.
46. 46 Xu, Z.M., Tavares-Sanchez, O.L., Li, Q.Z., Fernando, J., Rodriguez, C.M., Studer, E.J., et al. Activation of bile acid biosynthesis by the p38 mitogen-activated protein kinase (MAPK): hepatocyte nuclear factor-4α phosphorylation by the p38 MAPK is required for cholesterol 7α-hydroxylase expression. J Biol Chem 282 (2007), 24607-24614.
47. 47 Chellappa, K., Jankova, L., Schnabl, J.M., Pan, S.Q., Brelivet, Y., Fung, C.L.S., et al. Src tyrosine kinase phosphorylation of nuclear receptor HNF4α correlates with isoform-specific loss of HNF4α in human colon cancer. Proc Natl Acad Sci U S A 109 (2012), 2302-2307.
48. 48 Sun, K., Montana, V., Chellappa, K., Brelivet, Y., Moras, D., Maeda, Y., et al. Phosphorylation of a conserved serine in the deoxyribonucleic acid binding domain of nuclear receptors alters intracellular localization. Mol Endocrinol 21 (2007), 1297-1311.
49. 49 Viollet, B., Kahn, A., Raymondjean, M., Protein kinase A-dependent phosphorylation modulates DNA-binding activity of hepatocyte nuclear factor 4. Mol Cell Biol 17 (1997), 4208-4219.
50. 50 Dankel, S.N., Hoang, T., Flågeng, M.H., Sagen, J.V., Mellgren, G., cAMP-mediated regulation of HNF-4α depends on the level of coactivator PGC-1α. Biochim Biophys Acta 1803 (2010), 1013-1019.
51. 51 Yoon, J.C., Puigserver, P., Chen, G.X., Donovan, J., Wu, Z.D., Rhee, J., et al. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413 (2001), 131-138.
52. 52 Hong, Y.H., Varanasi, U.S., Yang, W.B., Leff, T., AMP-activated protein kinase regulates HNF4α transcriptional activity by inhibiting dimer formation and decreasing protein stability. J Biol Chem 278 (2003), 27495-27501.
53. 53 Wang, J.C., Stafford, J.M., Granner, D.K., SRC-1 and GRIP1 coactivate transcription with hepatocyte nuclear factor 4. J Biol Chem 273 (1998), 30847-30850.
54. 54 Lee, Y.K., Dell, H., Dowhan, D.H., Hadzopoulou-Cladaras, M., Moore, D.D., The orphan nuclear receptor SHP inhibits hepatocyte nuclear factor 4 and retinoid X receptor transactivation: two mechanisms for repression. Mol Cell Biol 20 (2000), 187-195.
55. 55 Martinez-Jimenez, C.P., Kyrmizi, I., Cardot, P., Gonzalez, F.J., Talianidis, I., Hepatocyte nuclear factor 4α coordinates a transcription factor network regulating hepatic fatty acid metabolism. Mol Cell Biol 30 (2010), 565-577.
56. 56 Kim, S.C., Kim, C.K., Axe, D., Cook, A., Lee, M., Li, T.G., et al. All-trans-retinoic acid ameliorates hepatic steatosis in mice by a novel transcriptional cascade. Hepatology 59 (2014), 1750-1760.
57. 57 Zhang, Y.X., Hagedorn, C.H., Wang, L., Role of nuclear receptor SHP in metabolism and cancer. Biochim Biophys Acta 1812 (2011), 893-908.
58. 58 Zhang, Y.X., Wang, L., Characterization of the mitochondrial localization of the nuclear receptor SHP and regulation of its subcellular distribution by interaction with Bcl2 and HNF4α. PLoS One, 8, 2013, e68491.
59. 59 Zhang, Y.X., Soto, J., Park, K., Viswanath, G., Kuwada, S., Abel, E.D., et al. Nuclear receptor SHP, a death receptor that targets mitochondria, induces apoptosis and inhibits tumor growth. Mol Cell Biol 30 (2010), 1341-1356.
60. 60 Lee, J., Padhye, A., Sharma, A., Song, G.S., Miao, J., Mo, Y.Y., et al. A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via microRNA-34a inhibition. J Biol Chem 285 (2010), 12604-12611.
61. 61 Walesky, C., Edwards, G., Borude, P., Gunewardena, S., O׳Neil, M., Yoo, B., et al. Hepatocyte nuclear factor 4 alpha deletion promotes diethylnitrosamine-induced hepatocellular carcinoma in rodents. Hepatology 57 (2013), 2480-2490.
62. 62 Kliewer, S.A., Mangelsdorf, D.J., Bile acids as hormones: the FXR-FGF15/19 pathway. Dig Dis 33 (2015), 327-331.
63. 63 Staudinger, J.L., Goodwin, B., Jones, S.A., Hawkins-Brown, D., MacKenzie, K.I., LaTour, A., et al. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A 98 (2001), 3369-3374.
64. 64 Iwazaki, N., Kobayashi, K., Morimoto, K., Hirano, M., Kawashima, S., Furihata, T., et al. Involvement of hepatocyte nuclear factor 4α in transcriptional regulation of the human pregnane X receptor gene in the human liver. Drug Metab Pharmacokinet 23 (2008), 59-66.
65. 65 Kamiya, A., Inoue, Y., Gonzalez, F.J., Role of the hepatocyte nuclear factor 4α in control of the pregnane X receptor during fetal liver development. Hepatology 37 (2003), 1375-1384.
66. 66 Jung, D., Mangelsdorf, D.J., Meyer, U.A., Pregnane X receptor is a target of farnesoid X receptor. J Biol Chem 281 (2006), 19081-19091.
67. 67 Amador-Noguez, D., Dean, A., Huang, W., Setchell, K., Moore, D., Darlington, G., Alterations in xenobiotic metabolism in the long-lived Little mice. Aging Cell 6 (2007), 453-470.
68. 68 Wiwi, C.A., Gupte, M., Waxman, D.J., Sexually dimorphic P450 gene expression in liver-specific hepatocyte nuclear factor 4α-deficient mice. Mol Endocrinol 18 (2004), 1975-1987.
69. 69 Caron, S., Huaman Samanez, C., Dehondt, H., Ploton, M., Briand, O., Lien, F., et al. Farnesoid X receptor inhibits the transcriptional activity of carbohydrate response element binding protein in human hepatocytes. Mol Cell Biol 33 (2013), 2202-2211.
70. 70 Claudel, T., Inoue, Y., Barbier, O., Duran-Sandoval, D., Kosykh, V., Fruchart, J., et al. Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression. Gastroenterology 125 (2003), 544-555.
71. 71 Pineda Torra, I., Jamshidi, Y., Flavell, D.M., Fruchart, J.C., Staels, B., Characterization of the human PPARα promoter: identification of a functional nuclear receptor response element. Mol Endocrinol 16 (2002), 1013-1028.
72. 72 Chamouton, J., Latruffe, N., PPARα/HNF4α interplay on diversified responsive elements. Relevance in the regulation of liver peroxisomal fatty acid catabolism. Curr Drug Metab 13 (2012), 1436-1453.
73. 73 Nishiyama, C., Hi, R., Osada, S., Osumi, T., Functional interactions between nuclear receptors recognizing a common sequence element, the direct repeat motif spaced by one nucleotide (DR-1). J Biochem 123 (1998), 1174-1179.
74. 74 Dongol, B., Shah, Y., Kim, I., Gonzalez, F.J., Hunt, M.C., The acyl-CoA thioesterase I is regulated by PPARα and HNF4α via a distal response element in the promoter. J Lipid Res 48 (2007), 1781-1791.
75. 75 Winrow, C.J., Marcus, S.L., Miyata, K.S., Zhang, B., Capone, J.P., Rachubinski, R.A., Transactivation of the peroxisome proliferator-activated receptor is differentially modulated by hepatocyte nuclear factor-4. Gene Expr 4 (1994), 53-62.
76. 76 Cheng, X.G., Klaassen, C.D., Critical role of PPAR-α in perfluorooctanoic acid-and perfluorodecanoic acid-induced downregulation of Oatp uptake transporters in mouse livers. Toxicol Sci 106 (2008), 37-45.
77. 77 Rakhshandehroo, M., Knoch, B., Müller, M., Kersten, S., Peroxisome proliferator-activated receptor alpha target genes. PPAR Res, 2010, 2010, 612089.
78. 78 Klaassen, C., Lu, H., Xenobiotic receptors CAR and PXR. Bunce, C.M., Campbell, M.J., (eds.) Nuclear receptors: current concepts and future challenges, 2010, Springer, Netherlands, 287-305.
79. 79 Ding, X.S., Lichti, K., Kim, I., Gonzalez, F.J., Staudinger, J.L., Regulation of constitutive androstane receptor and its target genes by fasting, cAMP, hepatocyte nuclear factor α, and the coactivator peroxisome proliferator-activated receptor γ coactivator-1α. J Biol Chem 281 (2006), 26540-26551.
80. 80 Chen, Y.P., Kissling, G., Negishi, M., Goldstein, J.A., The nuclear receptors constitutive androstane receptor and pregnane X receptor cross-talk with hepatic nuclear factor 4α to synergistically activate the human CYP2C9 promoter. J Pharmacol Exp Ther 314 (2005), 1125-1133.
81. 81 Echchgadda, I., Song, C.S., Oh, T., Ahmed, M., De La Cruz, I.J., Chatterjee, B., 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 (2007), 2099-2111.
82. 82 Miao, J., Fang, S.S., Bae, Y., Kemper, J.K., Functional inhibitory cross-talk between constitutive androstane receptor and hepatic nuclear factor-4 in hepatic lipid/glucose metabolism is mediated by competition for binding to the DR1 motif and to the common coactivators, GRIP-1 and PGC-1α. J Biol Chem 281 (2006), 14537-14546.
83. 83 Li, T.G., Chiang, J.Y.L., Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7α-hydroxylase gene transcription. Am J Physiol Gastrointest Liver Physiol 288 (2005), G74-G84.
84. 84 Cave, M.C., Clair, H.B., Hardesty, J.E., Falkner, K.C., Feng, W.K., Clark, B.J., et al. Nuclear receptors and nonalcoholic fatty liver disease. Biochim Biophys Acta, 2016 Available from: http://dx.doi.org/10.1016/j.bbagrm.2016.03.002.
85. 85 Kandel, B.A., Thomas, M., Winter, S., Damm, G., Seehofer, D., Burk, O., et al. Genomewide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPARα in primary human hepatocytes. Biochim Biophys Acta, 2016 Available from: http://dx.doi.org/10.1016/j.bbagrm.2016.03.007.
86. 86 Wang, S.H., Yeh, S.H., Lin, W.H., Yeh, K.H., Yuan, Q., Xia, N.S., et al. Estrogen receptor α represses transcription of HBV genes via interaction with hepatocyte nuclear factor 4α. Gastroenterology 142 (2012), 989-998 . e4.
87. 87 Yamamoto, Y., Moore, R., Hess, H.A., Guo, G.L., Gonzalez, F.J., Korach, K.S., et al. Estrogen receptor α mediates 17α-ethynylestradiol causing hepatotoxicity. J Biol Chem 281 (2006), 16625-16631.
88. 88 Rufibach, L.E., Duncan, S.A., Battle, M., Deeb, S.S., Transcriptional regulation of the human hepatic lipase (LIPC) gene promoter. J Lipid Res 47 (2006), 1463-1477.
89. 89 You, M., Fischer, M., Cho, W.K., Crabb, D., Transcriptional control of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4: inhibition by cyclic AMP and COUP transcription factors. Arch Biochem Biophys 398 (2002), 79-86.
90. 90 Litchfield, L.M., Klinge, C.M., Multiple roles of COUP-TFII in cancer initiation and progression. J Mol Endocrinol 49 (2012), R135-R148.
91. 91 Stroup, D., HNF4, Chiang J.Y., and COUP-TFII interact to modulate transcription of the cholesterol 7α-hydroxylase gene (CYP7A1). J Lipid Res 41 (2000), 1-11.
92. 92 Ktistaki, E., Talianidis, I., Chicken ovalbumin upstream promoter transcription factors act as auxiliary cofactors for hepatocyte nuclear factor 4 and enhance hepatic gene expression. Mol Cell Biol 17 (1997), 2790-2797.
93. 93 Hwang-Verslues, W.W., Sladek, F.M., Nuclear receptor hepatocyte nuclear factor 4α1 competes with oncoprotein c-Myc for control of the p21/WAF1 promoter. Mol Endocrinol 22 (2008), 78-90.
94. 94 Hanse, E.A., Mashek, D.G., Becker, J.R., Solmonson, A.D., Mullany, L.K., Mashek, M.T., et al. Cyclin D1 inhibits hepatic lipogenesis via repression of carbohydrate response element binding protein and hepatocyte nuclear factor 4α. Cell Cycle 11 (2012), 2681-2690.
95. 95 Wang, C.G., Pattabiraman, N., Zhou, J.N., Fu, M.F., Sakamaki, T., Albanese, C., et al. Cyclin D1 repression of peroxisome proliferator-activated receptor γ expression and transactivation. Mol Cell Biol 23 (2003), 6159-6173.
96. 96 Mullany, L.K., White, P., Hanse, E.A., Nelsen, C.J., Goggin, M.M., Mullany, J.E., et al. Distinct proliferative and transcriptional effects of the D-type cyclins in vivo. Cell Cycle 7 (2008), 2215-2224.
97. 97 Gunewardena, S.S., Yoo, B., Peng, L., Lu, H., Zhong, X.B., Klaassen, C.D., et al. Deciphering the developmental dynamics of the mouse liver transcriptome. PLoS One, 10, 2015, e0141220.
98. 98 Derdak, Z., Villegas, K.A., Harb, R., Wu, A.M., Sousa, A., Wands, J.R., Inhibition of p53 attenuates steatosis and liver injury in a mouse model of non-alcoholic fatty liver disease. J Hepatol 58 (2013), 785-791.
99. 99 Schäfer, T., Scheuer, C., Roemer, K., Menger, M.D., Vollmar, B., Inhibition of p53 protects liver tissue against endotoxin-induced apoptotic and necrotic cell death. FASEB J 17 (2003), 660-667.
100. 100 Maeda, Y., Seidel, S.D., Wei, G., Liu, X., Sladek, F.M., Repression of hepatocyte nuclear factor 4α tumor suppressor p53: involvement of the ligand-binding domain and histone deacetylase activity. Mol Endocrinol 16 (2002), 402-410.
101. 101 Maeda, Y., Hwang-Verslues, W.W., Wei, G., Fukazawa, T., Durbin, M.L., Owen, L.B., et al. Tumour suppressor p53 down-regulates the expression of the human hepatocyte nuclear factor 4α (HNF4α) gene. Biochem J 400 (2006), 303-313.
102. 102 Takagi, S., Nakajima, M., Kida, K., Yamaura, Y., Fukami, T., Yokoi, T., MicroRNAs regulate human hepatocyte nuclear factor 4α, modulating the expression of metabolic enzymes and cell cycle. J Biol Chem 285 (2010), 4415-4422.
103. 103 Torre, C., Perret, C., Colnot, S., Transcription dynamics in a physiological process: β-catenin signaling directs liver metabolic zonation. Int J Biochem Cell Biol 43 (2011), 271-278.
104. 104 Colletti, M., Cicchini, C., Conigliaro, A., Santangelo, L., Alonzi, T., Pasquini, E., et al. Convergence of Wnt signaling on the HNF4α-driven transcription in controlling liver zonation. Gastroenterology 137 (2009), 660-672.
105. 105 Braeuning, A., Sanna, R., Huelsken, J., Schwarz, M., Inducibility of drug-metabolizing enzymes by xenobiotics in mice with liver-specific knockout of Ctnnb1. Drug Metab Dispos 37 (2009), 1138-1145.
106. 106 Stanulović, V.S., Kyrmizi, I., Kruithof-de Julio, M., Hoogenkamp, M., Vermeulen, J.L., Ruijter, J.M., et al. Hepatic HNF4α deficiency induces periportal expression of glutamine synthetase and other pericentral enzymes. Hepatology 45 (2007), 433-444.
107. 107 Walesky, C., Gunewardena, S., Terwilliger, E.F., Edwards, G., Borude, P., Apte, U., Hepatocyte-specific deletion of hepatocyte nuclear factor-4α in adult mice results in increased hepatocyte proliferation. Am J Physiol Gastrointest Liver Physiol 304 (2013), G26-G37.
108. 108 Teo, J.L., Kahn, M., The Wnt signaling pathway in cellular proliferation and differentiation: a tale of two coactivators. Adv Drug Deliv Rev 62 (2010), 1149-1155.
109. 109 Lenz, H.J., Kahn, M., Safely targeting cancer stem cells via selective catenin coactivator antagonism. Cancer Sci 105 (2014), 1087-1092.
110. 110 Eeckhoute, J., Formstecher, P., Laine, B., Hepatocyte nuclear factor 4α enhances the hepatocyte nuclear factor 1α-mediated activation of transcription. Nucleic Acids Res 32 (2004), 2586-2593.
111. 111 Forhead, A.J., Fowden, A.L., Thyroid hormones in fetal growth and prepartum maturation. J Endocrinol 221 (2014), R87-103.
112. 112 van der Heide, S.M., Joosten, B.J., Everts, M.E., Klaren, P.H., Activities of UDP-glucuronyltransferase, β-glucuronidase and deiodinase types I and II in hyper- and hypothyroid rats. J Endocrinol 181 (2004), 393-400.
113. 113 Nishio, N., Katsura, T., Ashida, K., Okuda, M., Inui, K.I., Modulation of P-glycoprotein expression in hyperthyroid rat tissues. Drug Metab Dispos 33 (2005), 1584-1587.
114. 114 Rosenberg, D.W., Drummond, G.S., Smith, T.J., Depletion of cytochrome P-450 by thyroid hormone and cobalt-protoporphyrin IX in rat liver: evidence that susceptibility varies among forms of the heme protein. Pharmacology 51 (1995), 254-262.
115. 115 Lu, H., Klaassen, C., Tissue distribution and thyroid hormone regulation of Pept1 and Pept2 mRNA in rodents. Peptides 27 (2006), 850-857.
116. 116 Huang, Y.Y., Gusdon, A.M., Qu, S., Cross-talk between the thyroid and liver: a new target for nonalcoholic fatty liver disease treatment. World J Gastroenterol 19 (2013), 8238-8246.
117. 117 Tee, M.K., Huang, N.W., Damm, I., Miller, W.L., Transcriptional regulation of the human P450 oxidoreductase gene: hormonal regulation and influence of promoter polymorphisms. Mol Endocrinol 25 (2011), 715-731.
118. 118 Ram, P.A., Waxman, D.J., Thyroid hormone stimulation of NADPH P450 reductase expression in liver and extrahepatic tissues. Regulation by multiple mechanisms. J Biol Chem 267 (1992), 3294-3301.
119. 119 Selva, D.M., Hammond, G.L., Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4α. J Mol Endocrinol 43 (2009), 19-27.
120. 120 Foti, D., Stroup, D., Chiang, J.Y., Basic transcription element binding protein (BTEB) transactivates the cholesterol 7α-hydroxylase gene (CYP7A). Biochem Biophys Res Commun 253 (1998), 109-113.
121. 121 Imataka, H., Sogawa, K., Yasumoto, K., Kikuchi, Y., Sasano, K., Kobayashi, A., et al. Two regulatory proteins that bind to the basic transcription element (BTE), a GC box sequence in the promoter region of the rat P-4501A1 gene. EMBO J 11 (1992), 3663-3671.
122. 122 Koh, K.H., Pan, X., Zhang, W., McLachlan, A., Urrutia, R., Jeong, H., Kruppel-like factor 9 promotes hepatic cytochrome P450 2D6 expression during pregnancy in CYP2D6-humanized mice. Mol Pharmacol 86 (2014), 727-735.
123. 123 Cvoro, A., Devito, L., Milton, F.A., Noli, L., Zhang, A.J., Filippi, C., et al. A thyroid hormone receptor/KLF9 axis in human hepatocytes and pluripotent stem cells. Stem Cells 33 (2015), 416-428.
124. 124 Ohguchi, H., Tanaka, T., Uchida, A., Magoori, K., Kudo, H., Kim, I., et al. Hepatocyte nuclear factor 4α contributes to thyroid hormone homeostasis by cooperatively regulating the type 1 iodothyronine deiodinase gene with GATA4 and Krüppel-like transcription factor 9. Mol Cell Biol 28 (2008), 3917-3931.
125. 125 Sun, J.B., Wang, B.S., Liu, Y., Zhang, L., Ma, A.H., Yang, Z.J., et al. Transcription factor KLF9 suppresses the growth of hepatocellular carcinoma cells in vivo and positively regulates p53 expression. Cancer Lett 355 (2014), 25-33.
126. 126 Kimura, H., Fujimori, K., Activation of early phase of adipogenesis through Krüppel-like factor KLF9-mediated, enhanced expression of CCAAT/enhancer-binding protein β in 3T3-L1 cells. Gene 534 (2014), 169-176.
127. 127 Escalona-Nandez, I., Guerrero-Escalera, D., Estanes-Hernández, A., Ortíz-Ortega, V., Tovar, A.R., Pérez-Monter, C., The activation of peroxisome proliferator-activated receptor γ is regulated by Krüppel-like transcription factors 6 & 9 under steatotic conditions. Biochem Biophys Res Commun 458 (2015), 751-756.
128. 128 Chen, A.P., Davis, B.H., The DNA binding protein BTEB mediates acetaldehyde-induced, jun N-terminal kinase-dependent αI(I) collagen gene expression in rat hepatic stellate cells. Mol Cell Biol 20 (2000), 2818-2826.
129. 129 Fabregat, I., Moreno-Càceres, J., Sánchez, A., Dooley, S., Dewidar, B., Giannelli, G., et al. TGF-β signaling and liver disease. FEBS J, 2016 . Available from: http://dx.doi.org/10.1111/febs.13665.
130. 130 Karkampouna, S., ten Dijke, P., Dooley, S., Kruithof-de Julio, M., TGFβ signaling in liver regeneration. Curr Pharm Des 18 (2012), 4103-4113.
131. 131 Cozzolino, A.M., Alonzi, T., Santangelo, L., Mancone, C., Conti, B., Steindler, C., et al. TGFβ overrides HNF4α tumor suppressing activity through GSK3β inactivation: implication for hepatocellular carcinoma gene therapy. J Hepatol 58 (2013), 65-72.
132. 132 de Lucas, S., López-Alcorocho, J.M., Bartolomé, J., Carreño, V., Nitric oxide and TGF-β1 inhibit HNF-4α function in HEPG2 cells. Biochem Biophys Res Commun 321 (2004), 688-694.
133. 133 Chou, W.C., Prokova, V., Shiraishi, K., Valcourt, U., Moustakas, A., Hadzopoulou-Cladaras, M., et al. Mechanism of a transcriptional cross talk between transforming growth factor-β-regulated Smad3 and Smad4 proteins and orphan nuclear receptor hepatocyte nuclear factor-4. Mol Biol Cell 14 (2003), 1279-1294.
134. 134 Kardassis, D., Pardali, K., Zannis, V.I., SMAD proteins transactivate the human ApoCIII promoter by interacting physically and functionally with hepatocyte nuclear factor 4. J Biol Chem 275 (2000), 41405-41414.
135. 135 Li, T.G., Chiang, J.Y., A novel role of transforming growth factor β1 in transcriptional repression of human cholesterol 7α-hydroxylase gene. Gastroenterology 133 (2007), 1660-1669.
136. 136 Mizutani, A., Koinuma, D., Tsutsumi, S., Kamimura, N., Morikawa, M., Suzuki, H.I., et al. Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4α in HepG2 cells. J Biol Chem 286 (2011), 29848-29860.
137. 137 Yang, L., Roh, Y.S., Song, J.Y., Zhang, B., Liu, C., Loomba, R., et al. Transforming growth factor beta signaling in hepatocytes participates in steatohepatitis through regulation of cell death and lipid metabolism in mice. Hepatology 59 (2014), 483-495.
138. 138 Chia, S.M., Lin, P.C., Yu, H., TGF-β1 regulation in hepatocyte-NIH3T3 co-culture is important for the enhanced hepatocyte function in 3D microenvironment. Biotechnol Bioeng 89 (2005), 565-573.
139. 139 Friedbichler, K., Themanns, M., Mueller, K.M., Schlederer, M., Kornfeld, J.W., Terracciano, L.M., et al. Growth-hormone-induced signal transducer and activator of transcription 5 signaling causes gigantism, inflammation, and premature death but protects mice from aggressive liver cancer. Hepatology 55 (2012), 941-952.
140. 140 Eicher, E.M., Beamer, W.G., Inherited ateliotic dwarfism in mice. Characteristics of the mutation, little, on chromosome 6. J Hered 67 (1976), 87-91.
141. 141 Hahn, T.M., Copeland, K.C., Woo, S.L., Phenotypic correction of dwarfism by constitutive expression of growth hormone. Endocrinology 137 (1996), 4988-4993.
142. 142 Noshiro, M., Negishi, M., Pretranslational regulation of sex-dependent testosterone hydroxylases by growth hormone in mouse liver. J Biol Chem 261 (1986), 15923-15927.
143. 143 Morgan, E.T., MacGeoch, C., Gustafsson, J.A., Hormonal and developmental regulation of expression of the hepatic microsomal steroid 16 alpha-hydroxylase cytochrome P-450 apoprotein in the rat. J Biol Chem 260 (1985), 11895-11898.
144. 144 Sharma, M.C., Agrawal, A.K., Sharma, M.R., Shapiro, B.H., Interactions of gender, growth hormone, and phenobarbital induction on murine Cyp2b expression. Biochem Pharmacol 56 (1998), 1251-1258.
145. 145 Cheng, X.G., Buckley, D., Klaassen, C.D., Regulation of hepatic bile acid transporters Ntcp and Bsep expression. Biochem Pharmacol 74 (2007), 1665-1676.
146. 146 Cheng, X.G., Maher, J., Lu, H., Klaassen, C.D., Endocrine regulation of gender-divergent mouse organic anion-transporting polypeptide (Oatp) expression. Mol Pharmacol 70 (2006), 1291-1297.
147. 147 Baik, M., Yu, J.H., Hennighausen, L., Growth hormone-STAT5 regulation of growth, hepatocellular carcinoma, and liver metabolism. Ann NY Acad Sci 1229 (2011), 29-37.
148. 148 Koschmieder, S., Mughal, T.I., Hasselbalch, H.C., Barosi, G., Valent, P., Kiladjian, J.J., et al. Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both. Leukemia 30 (2016), 1018-1024.
149. 149 Park, S.H., Wiwi, C.A., Waxman, D.J., Signalling cross-talk between hepatocyte nuclear factor 4α and growth-hormone-activated STAT5b. Biochem J 397 (2006), 159-168.
150. 150 Holloway, M.G., Laz, E.V., Waxman, D.J., Codependence of growth hormone-responsive, sexually dimorphic hepatic gene expression on signal transducer and activator of transcription 5b and hepatic nuclear factor 4α. Mol Endocrinol 20 (2006), 647-660.
151. 151 Rabkin, R., Sun, D.F., Chen, Y., Tan, J., Schaefer, F., Growth hormone resistance in uremia, a role for impaired JAK/STAT signaling. Pediatr Nephrol 20 (2005), 313-318.
152. 152 Schaefer, F., Chen, Y., Tsao, T., Nouri, P., Rabkin, R., Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia. J Clin Investig 108 (2001), 467-475.
153. 153 Velenosi, T.J., Feere, D.A., Sohi, G., Hardy, D.B., Urquhart, B.L., Decreased nuclear receptor activity and epigenetic modulation associates with down-regulation of hepatic drug-metabolizing enzymes in chronic kidney disease. FASEB J 28 (2014), 5388-5397.
154. 154 Dreisbach, A.W., Lertora, J.J., The effect of chronic renal failure on drug metabolism and transport. Expert Opin Drug Metab Toxicol 4 (2008), 1065-1074.
155. 155 Reiss, A.B., Voloshyna, I., De Leon, J., Miyawaki, N., Mattana, J., Cholesterol metabolism in CKD. Am J Kidney Dis 66 (2015), 1071-1082.
156. 156 Engblom, D., Kornfeld, J.W., Schwake, L., Tronche, F., Reimann, A., Beug, H., et al. Direct glucocorticoid receptor-Stat5 interaction in hepatocytes controls body size and maturation-related gene expression. Genes Dev 21 (2007), 1157-1162.
157. 157 Tronche, F., Opherk, C., Moriggl, R., Kellendonk, C., Reimann, A., Schwake, L., et al. Glucocorticoid receptor function in hepatocytes is essential to promote postnatal body growth. Genes Dev 18 (2004), 492-497.
158. 158 Mueller, K.M., Kornfeld, J.W., Friedbichler, K., Blaas, L., Egger, G., Esterbauer, H., et al. Impairment of hepatic growth hormone and glucocorticoid receptor signaling causes steatosis and hepatocellular carcinoma in mice. Hepatology 54 (2011), 1398-1409.
159. 159 Bailly, A., Briançon, N., Weiss, M.C., Characterization of glucocorticoid receptor and hepatocyte nuclear factor 4α (HNF4α) binding to the hnf4α gene in the liver. Biochimie 91 (2009), 1095-1103.
160. 160 Stafford, J.M., Wilkinson, J.C., Beechem, J.M., Granner, D.K., Accessory factors facilitate the binding of glucocorticoid receptor to the phosphoenolpyruvate carboxykinase gene promoter. J Biol Chem 276 (2001), 39885-39891.
161. 161 Onica, T., Nichols, K., Larin, M., Ng, L., Maslen, A., Dvorak, Z., et al. Dexamethasone-mediated up-regulation of human CYP2A6 involves the glucocorticoid receptor and increased binding of hepatic nuclear factor 4α to the proximal promoter. Mol Pharmacol 73 (2008), 451-460.
162. 162 Rulcova, A., Krausova, L., Smutny, T., Vrzal, R., Dvorak, Z., Jover, R., et al. Glucocorticoid receptor regulates organic cation transporter 1 (OCT1, SLC22A1) expression via HNF4α upregulation in primary human hepatocytes. Pharmacol Rep 65 (2013), 1322-1335.
163. 163 Xie, X.F., Liao, H.L., Dang, H.X., Pang, W., Guan, Y.F., Wang, X., et al. Down-regulation of hepatic HNF4α gene expression during hyperinsulinemia via SREBPs. Mol Endocrinol 23 (2009), 434-443.
164. 164 Yamamoto, T., Shimano, H., Nakagawa, Y., Ide, T., Yahagi, N., Matsuzaka, T., et al. SREBP-1 interacts with hepatocyte nuclear factor-4α and interferes with PGC-1 recruitment to suppress hepatic gluconeogenic genes. J Biol Chem 279 (2004), 12027-12035.
165. 165 Hirota, K., Daitoku, H., Matsuzaki, H., Araya, N., Yamagata, K., Asada, S., et al. Hepatocyte nuclear factor-4 is a novel downstream target of insulin via FKHR as a signal-regulated transcriptional inhibitor. J Biol Chem 278 (2003), 13056-13060.
166. 166 Simó, R., Barbosa-Desongles, A., Hernandez, C., Selva, D.M., IL1β down-regulation of sex hormone-binding globulin production by decreasing HNF-4α via MEK-1/2 and JNK MAPK pathways. Mol Endocrinol 26 (2012), 1917-1927.
167. 167 Mogilenko, D.A., Dizhe, E.B., Shavva, V.S., Lapikov, I.A., Orlov, S.V., Perevozchikov, A.P., Role of the nuclear receptors HNF4α, PPARα, and LXRs in the TNFα-mediated inhibition of human apolipoprotein A-I gene expression in HepG2 cells. Biochemistry 48 (2009), 11950-11960.
168. 168 Nikolaidou-Neokosmidou, V., Zannis, V.I., Kardassis, D., Inhibition of hepatocyte nuclear factor 4 transcriptional activity by the nuclear factor κB pathway. Biochem J 398 (2006), 439-450.
169. 169 Hatziapostolou, M., Polytarchou, C., Aggelidou, E., Drakaki, A., Poultsides, G.A., Jaeger, S.A., et al. An HNF4α-miRNA inflammatory feedback circuit regulates hepatocellular oncogenesis. Cell 147 (2011), 1233-1247.
170. 170 Liu, H.M., Lou, G.Y., Li, C.Y., Wang, X.D., Cederbaum, A.I., Gan, L.X., et al. HBx inhibits CYP2E1 gene expression via downregulating HNF4α in human hepatoma cells. PLoS One, 9, 2014, e107913.
171. 171 Wu, Q., Liu, H.O., Liu, Y.D., Liu, W.S., Pan, D., Zhang, W.J., et al. Decreased expression of hepatocyte nuclear factor 4α (Hnf4α)/microRNA-122 (miR-122) axis in hepatitis B virus-associated hepatocellular carcinoma enhances potential oncogenic GALNT10 protein activity. J Biol Chem 290 (2015), 1170-1185.
172. 2 GXIIB regulate production of infectious hepatitis C virus. J Virol 88 (2014), 612-627.
173. 173 Qadri, I., Iwahashi, M., Kullak-Ublick, G.A., Simon, F.R., Hepatocyte nuclear factor (HNF) 1 and HNF4 mediate hepatic multidrug resistance protein 2 up-regulation during hepatitis C virus gene expression. Mol Pharmacol 70 (2006), 627-636.
174. 174 Wang, Z., Ceniccola, K., Florea, L., Wang, B.D., Lee, N.H., Kumar, A., Viral non-coding RNA inhibits HNF4α expression in HCV associated hepatocellular carcinoma. Infect Agent Cancer, 10, 2015, 19.
175. 175 Zhao, J., Tang, N., Wu, K.M., Dai, W.P., Ye, C.H., Shi, J., et al. MiR-21 simultaneously regulates ERK1 signaling in HSC activation and hepatocyte EMT in hepatic fibrosis. PLoS One, 9, 2014, e108005.
176. 176 McDaniel, K., Herrera, L., Zhou, T.H., Francis, H., Han, Y.Y., Levine, P., et al. The functional role of microRNAs in alcoholic liver injury. J Cell Mol Med 18 (2014), 197-207.
177. 177 Ning, B.F., Ding, J., Liu, J., Yin, C., Xu, W.P., Cong, W.M., et al. Hepatocyte nuclear factor 4α-nuclear factor-κB feedback circuit modulates liver cancer progression. Hepatology 60 (2014), 1607-1619.
178. 12 gep oncogene deregulation of p53-responsive microRNAs promotes epithelial-mesenchymal transition of hepatocellular carcinoma. Oncogene 34 (2015), 2910-2921.
179. 12 overexpressed in hepatocellular carcinoma reduces microRNA-122 expression via HNF4α inactivation, which causes c-Met induction. Oncotarget 6 (2015), 19055-19069.
180. 180 Wortham, M., Czerwinski, M., He, L., Parkinson, A., Wan, Y.J., Expression of constitutive androstane receptor, hepatic nuclear factor 4α, 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 (2007), 1700-1710.
181. 181 Kamiyama, Y., Matsubara, T., Yoshinari, K., Nagata, K., Kamimura, H., Yamazoe, Y., 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 (2007), 287-298.
182. 182 Gonzalez, F.J., The 2006 bernard B. Brodie Award lecture. CYP2E1. Drug Metab Dispos 35 (2007), 1-8.
183. 183 Alnouti, Y., Bile acid sulfation: a pathway of bile acid elimination and detoxification. Toxicol Sci 108 (2009), 225-246.
184. 184 James, M.O., Ambadapadi, S., Interactions of cytosolic sulfotransferases with xenobiotics. Drug Metab Rev 45 (2013), 401-414.
185. 185 Fang, H.L., Strom, S.C., Ellis, E., Duanmu, Z., Fu, J.Q., Duniec-Dmuchowski, Z., et al. Positive and negative regulation of human hepatic hydroxysteroid sulfotransferase (SULT2A1) gene transcription by rifampicin: roles of hepatocyte nuclear factor 4α and pregnane X receptor. J Pharmacol Exp Ther 323 (2007), 586-598.
186. 186 Duanmu, Z., Weckle, A., Koukouritaki, S.B., Hines, R.N., Falany, J.L., Falany, C.N., et al. Developmental expression of aryl, estrogen, and hydroxysteroid sulfotransferases in pre- and postnatal human liver. J Pharmacol Exp Ther 316 (2006), 1310-1317.
187. 187 Alnouti, Y., Klaassen, C.D., Mechanisms of gender-specific regulation of mouse sulfotransferases (Sults). Xenobiotica 41 (2011), 187-197.
188. 188 Bathena, S.P.R., Mukherjee, S., Olivera, M., Alnouti, Y., The profile of bile acids and their sulfate metabolites in human urine and serum. J Chromatogr B 942-943 (2013), 53-62.
189. 189 Huang, J.G., Bathena, S.P., Csanaky, I.L., Alnouti, Y., Simultaneous characterization of bile acids and their sulfate metabolites in mouse liver, plasma, bile, and urine using LC-MS/MS. J Pharm Biomed Anal 55 (2011), 1111-1119.
190. 190 Longo, M., Crosignani, A., Podda, M., Hyperlipidemia in chronic cholestatic liver disease. Curr Treat Options Gastroenterol 4 (2001), 111-114.
191. 191 Yin, L.Y., Ma, H.Y., Ge, X.M., Edwards, P.A., Zhang, Y.Q., Hepatic hepatocyte nuclear factor 4α is essential for maintaining triglyceride and cholesterol homeostasis. Arterioscler Thromb Vasc Biol 31 (2011), 328-336.
192. 192 Bulla, G.A., Givens, E., Brown, S., Oladiran, B., Kraus, D., A common regulatory locus affects both HNF4/HNF1α pathway activation and sensitivity to LPS-mediated apoptosis in rat hepatoma cells. J Cell Sci 114 (2001), 1205-1212.
193. 193 Cattin, A.L., Le Beyec, J., Barreau, F., Saint-Just, S., Houllier, A., Gonzalez, F.J., et al. Hepatocyte nuclear factor 4α, a key factor for homeostasis, cell architecture, and barrier function of the adult intestinal epithelium. Mol Cell Biol 29 (2009), 6294-6308.
194. 194 Ahn, S.H., Shah, Y.M., Inoue, J., Morimura, K., Kim, I., Yim, S., et al. Hepatocyte nuclear factor 4α in the intestinal epithelial cells protects against inflammatory bowel disease. Inflamm Bowel Dis 14 (2008), 908-920.
195. 195 Barson, J.R., Karatayev, O., Chang, G.Q., Johnson, D.F., Bocarsly, M.E., Hoebel, B.G., et al. Positive relationship between dietary fat, ethanol intake, triglycerides, and hypothalamic peptides: counteraction by lipid-lowering drugs. Alcohol 43 (2009), 433-441.
196. 196 Klop, B., do Rego, A.T., Cabezas, M.C., Alcohol and plasma triglycerides. Curr Opin Lipidol 24 (2013), 321-326.
197. 197 Bertola, A., Mathews, S., Ki, S.H., Wang, H., Gao, B., Mouse model of chronic and binge ethanol feeding (the NIAAA model). Nat Protoc 8 (2013), 627-637.
198. 198 Cai, D.S., Yuan, M.S., Frantz, D.F., Melendez, P.A., Hansen, L., Lee, J., et al. Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κB. Nat Med 11 (2005), 183-190.
199. 199 Wieser, V., Adolph, T.E., Enrich, B., Kuliopulos, A., Kaser, A., Tilg, H., et al. Reversal of murine alcoholic steatohepatitis by pepducin-based functional blockade of interleukin-8 receptors. Gut, 2016 . Available from: http://dx.doi.org/10.1136/gutjnl-2015-310344.
200. 200 Battle, M.A., Konopka, G., Parviz, F., Gaggl, A.L., Yang, C.H., Sladek, F.M., et al. Hepatocyte nuclear factor 4α orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver. Proc Natl Acad Sci U S A 103 (2006), 8419-8424.
201. 201 Parviz, F., Matullo, C., Garrison, W.D., Savatski, L., Adamson, J.W., Ning, G., et al. Hepatocyte nuclear factor 4α controls the development of a hepatic epithelium and liver morphogenesis. Nat Genet 34 (2003), 292-296.
202. 202 Saghir, S.A., Khan, S.A., McCoy, A.T., Ontogeny of mammalian metabolizing enzymes in humans and animals used in toxicological studies. Crit Rev Toxicol 42 (2012), 323-357.
203. 203 Lu, H., Gunewardena, S., Cui, J.Y., Yoo, B., Zhong, X.B., Klaassen, C.D., RNA-sequencing quantification of hepatic ontogeny and tissue distribution of mRNAs of phase II enzymes in mice. Drug Metab Dispos 41 (2013), 844-857.
204. 204 Herrera, E., Amusquivar, E., Lipid metabolism in the fetus and the newborn. Diabetes Metab Res Rev 16 (2000), 202-210.
205. 205 Renaud, H.J., Cui, Y.J., Lu, H., Zhong, X.B., Klaassen, C.D., Ontogeny of hepatic energy metabolism genes in mice as revealed by RNA-sequencing. PLoS One, 9, 2014, e104560.
206. 206 Li, L., Oropeza, C.E., Sainz, B. Jr, Uprichard, S.L., Gonzalez, F.J., McLachlan, A., Developmental regulation of hepatitis B virus biosynthesis by hepatocyte nuclear factor 4α. PLoS One, 4, 2009, e5489.
207. 207 Lindner, T., Gragnoli, C., Furuta, H., Cockburn, B.N., Petzold, C., Rietzsch, H., et al. Hepatic function in a family with a nonsense mutation (R154X) in the hepatocyte nuclear factor-4α/MODY1 gene. J Clin Investig 100 (1997), 1400-1405.
208. 208 Iwasaki, N., Ogata, M., Tomonaga, O., Kuroki, H., Kasahara, T., Yano, N., et al. Liver and kidney function in Japanese patients with maturity-onset diabetes of the young. Diabetes Care 21 (1998), 2144-2148.
209. 209 Zhu, Q., Yamagata, K., Miura, A., Shihara, N., Horikawa, Y., Takeda, J., et al. T130I mutation in HNF-4α gene is a loss-of-function mutation in hepatocytes and is associated with late-onset Type 2 diabetes mellitus in Japanese subjects. Diabetologia 46 (2003), 567-573.
210. 210 Shih, D.Q., Dansky, H.M., Fleisher, M., Assmann, G., Fajans, S.S., Stoffel, M., Genotype/phenotype relationships in HNF-4α/MODY1: haploinsufficiency is associated with reduced apolipoprotein(AII), apolipoprotein(CIII), lipoprotein(a), and triglyceride levels. Diabetes 49 (2000), 832-837.
211. 211 Pramfalk, C., Karlsson, E., Groop, L., Rudel, L.L., Angelin, B., Eriksson, M., et al. Control of ACAT2 liver expression by HNF4α: lesson from MODY1 patients. Arterioscler Thromb Vasc Biol 29 (2009), 1235-1241.
212. 212 Laine, B., Eeckhoute, J., Suaud, L., Briche, I., Furuta, H., Bell, G.I., et al. Functional properties of the R154X HNF-4α protein generated by a mutation associated with maturity-onset diabetes of the young, type 1. FEBS Lett 479 (2000), 41-45.
213. 213 Stoffel, M., Duncan, S.A., The maturity-onset diabetes of the young (MODY1) transcription factor HNF4α regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci U S A 94 (1997), 13209-13214.
214. 214 Ogata, M., Awaji, T., Iwasaki, N., Fujimaki, R., Takizawa, M., Maruyama, K., et al. Localization of hepatocyte nuclear factor-4α in the nucleolus and nucleus is regulated by its C-terminus. J Diabetes Investig 3 (2012), 449-456.