Hepatic Nuclear Factor 1 Alpha (HNF-1α) In Human Physiology and Molecular Medicine

Author(s): Sumreen Begum*

Journal Name: Current Molecular Pharmacology

Volume 13 , Issue 1 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


The transcription factors (TFs) play a crucial role in the modulation of specific gene transcription networks. One of the hepatocyte nuclear factors (HNFs) family’s member, hepatocyte nuclear factor-1α (HNF-1α) has continuously become a principal TF to control the expression of genes. It is involved in the regulation of a variety of functions in various human organs including liver, pancreas, intestine, and kidney. It regulates the expression of enzymes involved in endocrine and xenobiotic activity through various metabolite transporters located in the above organs. Its expression is also required for organ-specific cell fate determination. Despite two decades of its first identification in hepatocytes, a review of its significance was not comprehended. Here, the role of HNF-1α in the above organs at the molecular level to intimate molecular mechanisms for regulating certain gene expression whose malfunctions are attributed to the disease conditions has been specifically encouraged. Moreover, the epigenetic effects of HNF-1α have been discussed here, which could help in advanced technologies for molecular pharmacological intervention and potential clinical implications for targeted therapies.

HNF-1α plays an indispensable role in several physiological mechanisms in the liver, pancreas, intestine, and kidney. Loss of its operations leads to the non-functional or abnormal functional state of each organ. Specific molecular agents or epigenetic modifying drugs that reactivate HNF-1α are the current requirements for the medications of the diseases.

Keywords: Hepatic nuclear factor-1α, MODY3, SLC, SGLT, URAT-1, HCC, Epigenetics.

Lau, H.H.; Ng, N.H.J.; Loo, L.S.W.; Jasmen, J.B.; Teo, A.K.K. The molecular functions of hepatocyte nuclear factors - In and beyond the liver. J. Hepatol., 2018, 68(5), 1033-1048.
[http://dx.doi.org/10.1016/j.jhep.2017.11.026] [PMID: 29175243]
Párrizas, M.; Maestro, M.A.; Boj, S.F.; Paniagua, A.; Casamitjana, R.; Gomis, R.; Rivera, F.; Ferrer, J. Hepatic nuclear factor 1-alpha directs nucleosomal hyperacetylation to its tissue-specific transcriptional targets. Mol. Cell. Biol., 2001, 21(9), 3234-3243.
[http://dx.doi.org/10.1128/MCB.21.9.3234-3243.2001] [PMID: 11287626]
D’Angelo, A.; Bluteau, O.; Garcia-Gonzalez, M.A.; Gresh, L.; Doyen, A.; Garbay, S.; Robine, S.; Pontoglio, M. Hepatocyte nuclear factor 1α and β control terminal differentiation and cell fate commitment in the gut epithelium. Development, 2010, 137(9), 1573-1582.
[http://dx.doi.org/10.1242/dev.044420] [PMID: 20388655]
Yang, R.; Kerschner, J.L.; Harris, A. Hepatocyte nuclear factor 1 coordinates multiple processes in a model of intestinal epithelial cell function. Biochim. Biophys. Acta, 2016, 1859(4), 591-598.
[http://dx.doi.org/10.1016/j.bbagrm.2016.02.005] [PMID: 26855178]
Bonzo, J.A.; Patterson, A.D.; Krausz, K.W.; Gonzalez, F.J. Metabolomics identifies novel Hnf1alpha-dependent physiological pathways in vivo. Mol. Endocrinol., 2010, 24(12), 2343-2355.
[http://dx.doi.org/10.1210/me.2010-0130] [PMID: 20943816]
Yu, M.; Wang, J.; Li, W.; Yuan, Y.Z.; Li, C.Y.; Qian, X.H.; Xu, W.X.; Zhan, Y.Q.; Yang, X.M. Proteomic screen defines the hepatocyte nuclear factor 1alpha-binding partners and identifies HMGB1 as a new cofactor of HNF1alpha. Nucleic Acids Res., 2008, 36(4), 1209-1219.
[http://dx.doi.org/10.1093/nar/gkm1131] [PMID: 18160415]
Vaxillaire, M.; Boccio, V.; Philippi, A.; Vigouroux, C.; Terwilliger, J.; Passa, P.; Beckmann, J.S.; Velho, G.; Lathrop, G.M.; Froguel, P. A gene for maturity onset diabetes of the young (MODY) maps to chromosome 12q. Nat. Genet., 1995, 9(4), 418-423.
[http://dx.doi.org/10.1038/ng0495-418] [PMID: 7795649]
Pelletier, L.; Rebouissou, S.; Paris, A.; Rathahao-Paris, E.; Perdu, E.; Bioulac-Sage, P.; Imbeaud, S.; Zucman-Rossi, J. Loss of hepatocyte nuclear factor 1alpha function in human hepatocellular adenomas leads to aberrant activation of signaling pathways involved in tumorigenesis. Hepatology, 2010, 51(2), 557-566.
[http://dx.doi.org/10.1002/hep.23362] [PMID: 20041408]
Zhang, C.; Xie, F.; Li, L.; Zhang, C.; Zhang, Y.; Ying, W.; Liu, L.; Yan, X.; Yin, F.; Zhang, L. Hepatocyte nuclear factor 1 alpha (HNF1A) regulates transcription of O-GlcNAc transferase in a negative feedback mechanism. FEBS Lett., 2019, 593(10), 1050-1060.
[http://dx.doi.org/10.1002/1873-3468.13381] [PMID: 30953348]
Tanaka, K.; Terryn, S.; Geffers, L.; Garbay, S.; Pontoglio, M.; Devuyst, O. The transcription factor HNF1α regulates expression of chloride-proton exchanger ClC-5 in the renal proximal tubule. Am. J. Physiol. Renal Physiol., 2010, 299(6), F1339-F1347.
[http://dx.doi.org/10.1152/ajprenal.00077.2010] [PMID: 20810608]
Pelletier, L.; Rebouissou, S.; Vignjevic, D.; Bioulac-Sage, P.; Zucman-Rossi, J. HNF1α inhibition triggers epithelial-mesenchymal transition in human liver cancer cell lines. BMC Cancer, 2011, 11(1), 427.
[http://dx.doi.org/10.1186/1471-2407-11-427] [PMID: 21975049]
Pontoglio, M.; Prié, D.; Cheret, C.; Doyen, A.; Leroy, C.; Froguel, P.; Velho, G.; Yaniv, M.; Friedlander, G. HNF1α controls renal glucose reabsorption in mouse and man. EMBO Rep., 2000, 1(4), 359-365.
[http://dx.doi.org/10.1093/embo-reports/kvd071] [PMID: 11269503]
Terryn, S.; Tanaka, K.; Lengelé, J-P.; Olinger, E.; Dubois-Laforgue, D.; Garbay, S.; Kozyraki, R.; Van Der Smissen, P.; Christensen, E.I.; Courtoy, P.J.; Bellanné-Chantelot, C.; Timsit, J.; Pontoglio, M.; Devuyst, O. Tubular proteinuria in patients with HNF1α mutations: HNF1α drives endocytosis in the proximal tubule. Kidney Int., 2016, 89(5), 1075-1089.
[http://dx.doi.org/10.1016/j.kint.2016.01.027] [PMID: 27083284]
Luco, R.F.; Maestro, M.A.; del Pozo, N.; Philbrick, W.M.; de la Ossa, P.P.; Ferrer, J. A conditional model reveals that induction of hepatocyte nuclear factor-1alpha in Hnf1alpha-null mutant beta-cells can activate silenced genes postnatally, whereas overexpression is deleterious. Diabetes, 2006, 55(8), 2202-2211.
[http://dx.doi.org/10.2337/db05-1534] [PMID: 16873682]
Kirkpatrick, C.L.; Wiederkehr, A.; Baquié, M.; Akhmedov, D.; Wang, H.; Gauthier, B.R.; Akerman, I.; Ishihara, H.; Ferrer, J.; Wollheim, C.B. Hepatic nuclear factor 1α (HNF1α) dysfunction down-regulates X-box-binding protein 1 (XBP1) and sensitizes β-cells to endoplasmic reticulum stress. J. Biol. Chem., 2011, 286(37), 32300-32312.
[http://dx.doi.org/10.1074/jbc.M111.247866] [PMID: 21784843]
Xie, R.; Carrano, A.C.; Sander, M. A systems view of epigenetic networks regulating pancreas development and β-cell function. Wiley Interdiscip. Rev. Syst. Biol. Med., 2015, 7(1), 1-11.
[http://dx.doi.org/10.1002/wsbm.1287] [PMID: 25644779]
Rebouissou, S.; Imbeaud, S.; Balabaud, C.; Boulanger, V.; Bertrand-Michel, J.; Tercé, F.; Auffray, C.; Bioulac-Sage, P.; Zucman-Rossi, J. HNF1α inactivation promotes lipogenesis in human hepatocellular adenoma independently of SREBP-1 and carbohydrate-response element-binding protein (ChREBP) activation. J. Biol. Chem., 2007, 282(19), 14437-14446.
[http://dx.doi.org/10.1074/jbc.M610725200] [PMID: 17379603]
Qian, H.; Deng, X.; Huang, Z.W.; Wei, J.; Ding, C.H.; Feng, R.X.; Zeng, X.; Chen, Y.X.; Ding, J.; Qiu, L.; Hu, Z.L.; Zhang, X.; Wang, H.Y.; Zhang, J.P.; Xie, W.F. An HNF1α-regulated feedback circuit modulates hepatic fibrogenesis via the crosstalk between hepatocytes and hepatic stellate cells. Cell Res., 2015, 25(8), 930-945.
[http://dx.doi.org/10.1038/cr.2015.84] [PMID: 26169608]
Shih, D.Q.; Bussen, M.; Sehayek, E.; Breslow, J.L.; Stoffel, M. Hnf-1α is an essential regulator of bile acid and plasma cholesterol metabolism. Diabetes, 2001, 50, A8.
Sucajtys-Szulc, E.; Debska-Slizien, A.; Rutkowski, B.; Milczarek, R.; Pelikant-Malecka, I.; Sledzinski, T.; Swierczynski, J.; Szolkiewicz, M. 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., 2018, 446(1-2), 11-23.
[http://dx.doi.org/10.1007/s11010-018-3268-1] [PMID: 29330688]
Matsui, C.; Deng, L.; Minami, N.; Abe, T.; Koike, K.; Shoji, I. Hepatitis C virus NS5A protein promotes the lysosomal degradation of hepatocyte nuclear factor 1alpha via chaperone-mediated autophagy. J. Virol., 2018, 92(13), e00639-e18.
[http://dx.doi.org/10.1128/JVI.00639-18] [PMID: 29695419]
Wang, H.; Maechler, P.; Hagenfeldt, K.A.; Wollheim, C.B. Dominant-negative suppression of HNF-1α function results in defective insulin gene transcription and impaired metabolism-secretion coupling in a pancreatic β-cell line. EMBO J., 1998, 17(22), 6701-6713.
[http://dx.doi.org/10.1093/emboj/17.22.6701] [PMID: 9822613]
Zucman-Rossi, J.; Jeannot, E.; Nhieu, J.T.; Scoazec, J.Y.; Guettier, C.; Rebouissou, S.; Bacq, Y.; Leteurtre, E.; Paradis, V.; Michalak, S.; Wendum, D.; Chiche, L.; Fabre, M.; Mellottee, L.; Laurent, C.; Partensky, C.; Castaing, D.; Zafrani, E.S.; Laurent-Puig, P.; Balabaud, C.; Bioulac-Sage, P. Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology, 2006, 43(3), 515-524.
[http://dx.doi.org/10.1002/hep.21068] [PMID: 16496320]
Lin, J.; Gu, C.; Shen, Z.; Liu, Y.; Wang, W.; Tao, S.; Cui, X.; Liu, J.; Xie, Y. Hepatocyte nuclear factor 1α downregulates HBV gene expression and replication by activating the NF-κB signaling pathway. PLoS One, 2017, 12(3)e0174017
[http://dx.doi.org/10.1371/journal.pone.0174017] [PMID: 28319127]
Huang, P.; He, Z.; Ji, S.; Sun, H.; Xiang, D.; Liu, C.; Hu, Y.; Wang, X.; Hui, L. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature, 2011, 475(7356), 386-389.
[http://dx.doi.org/10.1038/nature10116] [PMID: 21562492]
Huang, P.; Zhang, L.; Gao, Y.; He, Z.; Yao, D.; Wu, Z.; Cen, J.; Chen, X.; Liu, C.; Hu, Y.; Lai, D.; Hu, Z.; Chen, L.; Zhang, Y.; Cheng, X.; Ma, X.; Pan, G.; Wang, X.; Hui, L. Direct reprogramming of human fibroblasts to functional and expandable hepatocytes. Cell Stem Cell, 2014, 14(3), 370-384.
[http://dx.doi.org/10.1016/j.stem.2014.01.003] [PMID: 24582927]
Kim, J.; Kim, K-P.; Lim, K.T.; Lee, S.C.; Yoon, J.; Song, G.; Hwang, S.I.; Schöler, H.R.; Cantz, T.; Han, D.W. Generation of integration-free induced hepatocyte-like cells from mouse fibroblasts. Sci. Rep., 2015, 5, 15706.
[http://dx.doi.org/10.1038/srep15706] [PMID: 26503743]
Möbus, S.; Markovic, J.; Manns, M.P.; Ott, M.; Cantz, T.; Sharma, A.D. Functional microRNA screening to improve hepatocyte formation via direct reprogramming. Z. Gastroenterol., 2019, 57(01), 1-30.
Du, Y.; Wang, J.; Jia, J.; Song, N.; Xiang, C.; Xu, J.; Hou, Z.; Su, X.; Liu, B.; Jiang, T.; Zhao, D.; Sun, Y.; Shu, J.; Guo, Q.; Yin, M.; Sun, D.; Lu, S.; Shi, Y.; Deng, H. Human hepatocytes with drug metabolic function induced from fibroblasts by lineage reprogramming. Cell Stem Cell, 2014, 14(3), 394-403.
[http://dx.doi.org/10.1016/j.stem.2014.01.008] [PMID: 24582926]
Lim, K.T.; Lee, S.C.; Gao, Y.; Kim, K-P.; Song, G.; An, S.Y.; Adachi, K.; Jang, Y.J.; Kim, J.; Oh, K-J.; Kwak, T.H.; Hwang, S.I.; You, J.S.; Ko, K.; Koo, S.H.; Sharma, A.D.; Kim, J.H.; Hui, L.; Cantz, T.; Schöler, H.R.; Han, D.W. Small molecules facilitate single factor-mediated hepatic reprogramming. Cell Rep., 2016, 15(4), 814-829.
[http://dx.doi.org/10.1016/j.celrep.2016.03.071] [PMID: 27149847]
Ma, X.; Kong, L.; Zhu, S. Reprogramming cell fates by small molecules. Protein Cell, 2017, 8(5), 328-348.
[http://dx.doi.org/10.1007/s13238-016-0362-6] [PMID: 28213718]
Smith, S.B.; Gasa, R.; Watada, H.; Wang, J.; Griffen, S.C.; German, M.S. Neurogenin3 and hepatic nuclear factor 1 cooperate in activating pancreatic expression of Pax4. J. Biol. Chem., 2003, 278(40), 38254-38259.
[http://dx.doi.org/10.1074/jbc.M302229200] [PMID: 12837760]
Ellard, S. Hepatocyte nuclear factor 1 alpha (HNF-1 alpha) mutations in maturity-onset diabetes of the young. Hum. Mutat., 2000, 16(5), 377-385.
[http://dx.doi.org/10.1002/1098-1004(200011)16:5<377:AID-HUMU1>3.0.CO;2-2] [PMID: 11058894]
Kaisaki, P.J.; Menzel, S.; Lindner, T.; Oda, N.; Rjasanowski, I.; Sahm, J.; Meincke, G.; Schulze, J.; Schmechel, H.; Petzold, C.; Ledermann, H.M.; Sachse, G.; Boriraj, V.V.; Menzel, R.; Kerner, W.; Turner, R.C.; Yamagata, K.; Bell, G.I. Mutations in the hepatocyte nuclear factor-1α gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4. Diabetes, 1997, 46(3), 528-535.
[http://dx.doi.org/10.2337/diab.46.3.528] [PMID: 9032114]
Luni, C.; Marth, J.D.; Doyle, F.J., III Computational modeling of glucose transport in pancreatic β-cells identifies metabolic thresholds and therapeutic targets in diabetes. PLoS One, 2012, 7(12)e53130
[http://dx.doi.org/10.1371/journal.pone.0053130] [PMID: 23300881]
Pedersen, K.B.; Chhabra, K.H.; Nguyen, V.K.; Xia, H.; Lazartigues, E. The transcription factor HNF1α induces expression of angiotensin-converting enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter motifs. Biochim. Biophys. Acta, 2013, 1829(11), 1225-1235.
[http://dx.doi.org/10.1016/j.bbagrm.2013.09.007] [PMID: 24100303]
Zoldoš, V.; Horvat, T.; Novokmet, M.; Cuenin, C.; Mužinić, A.; Pučić, M.; Huffman, J.E.; Gornik, O.; Polašek, O.; Campbell, H.; Hayward, C.; Wright, A.F.; Rudan, I.; Owen, K.; McCarthy, M.I.; Herceg, Z.; Lauc, G. Epigenetic silencing of HNF1A associates with changes in the composition of the human plasma N-glycome. Epigenetics, 2012, 7(2), 164-172.
[http://dx.doi.org/10.4161/epi.7.2.18918] [PMID: 22395466]
Martagón, A.J.; Bello-Chavolla, O.Y.; Arellano-Campos, O.; Almeda-Valdés, P.; Walford, G.A.; Cruz-Bautista, I.; Gómez-Velasco, D.V.; Mehta, R.; Muñoz-Hernández, L.; Sevilla-González, M.; Viveros-Ruiz, T.L.; Ordoñez-Sánchez, M.L.; Rodríguez-Guillen, R.; Florez, J.C.; Tusié-Luna, M.T.; Aguilar-Salinas, C.A. Mexican carriers of the HNF1A p.E508K variant do not experience an enhanced response to sulfonylureas. Diabetes Care, 2018, 41(8), 1726-1731.
[http://dx.doi.org/10.2337/dc18-0384] [PMID: 29844095]
Gu, N.; Adachi, T.; Matsunaga, T.; Takeda, J.; Tsujimoto, G.; Ishihara, A.; Yasuda, K.; Tsuda, K. Mutant HNF-1α and mutant HNF-1β identified in MODY3 and MODY5 downregulate DPP-IV gene expression in Caco-2 cells. Biochem. Biophys. Res. Commun., 2006, 346(3), 1016-1023.
[http://dx.doi.org/10.1016/j.bbrc.2006.06.010] [PMID: 16781669]
Gu, N.; Tsuda, M.; Matsunaga, T.; Adachi, T.; Yasuda, K.; Ishihara, A.; Tsuda, K. Glucose regulation of dipeptidyl peptidase IV gene expression is mediated by hepatocyte nuclear factor-1α in epithelial intestinal cells. Clin. Exp. Pharmacol. Physiol., 2008, 35(12), 1433-1439.
[http://dx.doi.org/10.1111/j.1440-1681.2008.05015.x] [PMID: 18671716]
Luo, Z.; Li, Y.; Wang, H.; Fleming, J.; Li, M.; Kang, Y.; Zhang, R.; Li, D. Hepatocyte nuclear factor 1A (HNF1A) as a possible tumor suppressor in pancreatic cancer. PLoS One, 2015, 10(3)e0121082
[http://dx.doi.org/10.1371/journal.pone.0121082] [PMID: 25793983]
Bluteau, O.; Jeannot, E.; Bioulac-Sage, P.; Marqués, J.M.; Blanc, J.F.; Bui, H.; Beaudoin, J.C.; Franco, D.; Balabaud, C.; Laurent-Puig, P.; Zucman-Rossi, J. Bi-allelic inactivation of TCF1 in hepatic adenomas. Nat. Genet., 2002, 32(2), 312-315.
[http://dx.doi.org/10.1038/ng1001] [PMID: 12355088]
Yu, Y.; Liang, S.; Zhou, Y.; Li, S.; Li, Y.; Liao, W. HNF1A/CASC2 regulates pancreatic cancer cell proliferation through PTEN/Akt signaling. J. Cell. Biochem., 2019, 120(3), 2816-2827.
[http://dx.doi.org/10.1002/jcb.26395] [PMID: 28865121]
Lussier, C.R.; Brial, F.; Roy, S.A.; Langlois, M.J.; Verdu, E.F.; Rivard, N.; Perreault, N.; Boudreau, F. Loss of hepatocyte-nuclear-factor-1α impacts on adult mouse intestinal epithelial cell growth and cell lineages differentiation. PLoS One, 2010, 5(8)e12378
[http://dx.doi.org/10.1371/journal.pone.0012378] [PMID: 20808783]
von Wnuck Lipinski, K.; Sattler, K.; Peters, S.; Weske, S.; Keul, P.; Klump, H.; Heusch, G.; Göthert, J.R.; Levkau, B. Hepatocyte nuclear factor 1A is a cell-intrinsic transcription factor required for B cell differentiation and development in mice. J. Immunol., 2016, 196(4), 1655-1665.
[http://dx.doi.org/10.4049/jimmunol.1500897] [PMID: 26800876]
Subramanian, V.S.; Srinivasan, P.; Wildman, A.J.; Marchant, J.S.; Said, H.M. Molecular mechanism(s) involved in differential expression of vitamin C transporters along the intestinal tract. Am. J. Physiol. Gastrointest. Liver Physiol., 2017, 312(4), G340-G347.
[http://dx.doi.org/10.1152/ajpgi.00369.2016] [PMID: 27932501]
Locke, J.M. Saint-Martin Cc, Laver TW, Patel KA, Wood AR, Sharp SA, Ellard S, Bellanne-Chantelot C, Hattersley AT, Harries LW: The common HNF1A variant I27L is a modifier of age at diabetes diagnosis in HNF1A-MODY individuals. Diabetes, 2018, 67(9), 1903-1907.
[http://dx.doi.org/10.2337/db18-0133] [PMID: 29895593]
Cheret, C.; Doyen, A.; Yaniv, M.; Pontoglio, M. Hepatocyte nuclear factor 1 α controls renal expression of the Npt1-Npt4 anionic transporter locus. J. Mol. Biol., 2002, 322(5), 929-941.
[http://dx.doi.org/10.1016/S0022-2836(02)00816-1] [PMID: 12367519]
Pontoglio, M.; Barra, J.; Hadchouel, M.; Doyen, A.; Kress, C.; Bach, J.P.; Babinet, C.; Yaniv, M. Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome. Cell, 1996, 84(4), 575-585.
[http://dx.doi.org/10.1016/S0092-8674(00)81033-8] [PMID: 8598044]
Reimer, R.J.; Edwards, R.H. Organic anion transport is the primary function of the SLC17/type I phosphate transporter family. Pflugers Arch., 2004, 447(5), 629-635.
[http://dx.doi.org/10.1007/s00424-003-1087-y] [PMID: 12811560]
Kikuchi, R.; Kusuhara, H.; Hattori, N.; Kim, I.; Shiota, K.; Gonzalez, F.J.; Sugiyama, Y. Regulation of tissue-specific expression of the human and mouse urate transporter 1 gene by hepatocyte nuclear factor 1 α/β and DNA methylation. Mol. Pharmacol., 2007, 72(6), 1619-1625.
[http://dx.doi.org/10.1124/mol.107.039701] [PMID: 17855651]
Jutabha, P.; Anzai, N.; Kitamura, K.; Taniguchi, A.; Kaneko, S.; Yan, K.; Yamada, H.; Shimada, H.; Kimura, T.; Katada, T.; Fukutomi, T.; Tomita, K.; Urano, W.; Yamanaka, H.; Seki, G.; Fujita, T.; Moriyama, Y.; Yamada, A.; Uchida, S.; Wempe, M.F.; Endou, H.; Sakurai, H. Human sodium phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate. J. Biol. Chem., 2010, 285(45), 35123-35132.
[http://dx.doi.org/10.1074/jbc.M110.121301] [PMID: 20810651]
Oda, S.; Fukami, T.; Yokoi, T.; Nakajima, M. Epigenetic regulation is a crucial factor in the repression of UGT1A1 expression in the human kidney. Drug Metab. Dispos., 2013, 41(10), 1738-1743.
[http://dx.doi.org/10.1124/dmd.113.051201] [PMID: 23401472]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [50 - 56]
Pages: 7
DOI: 10.2174/1874467212666190930144349
Price: $65

Article Metrics

PDF: 22
PRC: 1