Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor
Open accessAbstract
The multidrug resistance-associated protein 2 (MRP2, ABCC2), mediates the efflux of several conjugated compounds across the apical membrane of the hepatocyte into the bile canaliculi. We identified MRP2 in a screen designed to isolate genes that are regulated by the farnesoid X-activated receptor (FXR, NR1H4). MRP2 mRNA levels were induced following treatment of human or rat hepatocytes with either naturally occurring (chenodeoxycholic acid) or synthetic (GW4064) FXR ligands. In addition, we have shown that MRP2 expression is regulated by the pregnane X receptor (PXR, NR1I2) and constitutive androstane receptor (CAR, NR1I3). Thus, treatment of rodent hepatocytes with PXR or CAR agonists results in a robust induction of MRP2 mRNA levels. The dexamethasone- and pregnenolone 16alpha-carbonitrile-dependent induction of MRP2 expression was not evident in hepatocytes derived from PXR null mice. In contrast, induction of MRP2 by phenobarbital, an activator of CAR, was comparable in wild-type and PXR null mice. An unusual 26-bp sequence was identified 440 bp upstream of the MRP2 transcription initiation site that contains an everted repeat of the AGTTCA hexad separated by 8 nucleotides (ER-8). PXR, CAR, and FXR bound with high affinity to this element as heterodimers with the retinoid X receptor alpha (RXRalpha, NR2B1). Luciferase reporter gene constructs containing 1 kb of the rat MRP2 promoter were prepared and transiently transfected into HepG2 cells. Luciferase activity was induced in a PXR-, CAR-, or FXR-dependent manner. Furthermore, the isolated ER-8 element was capable of conferring PXR, CAR, and FXR responsiveness on a heterologous thymidine kinase promoter. Mutation of the ER-8 element abolished the nuclear receptor response. These studies demonstrate that MRP2 is regulated by three distinct nuclear receptor signaling pathways that converge on a common response element in the 5'-flanking region of this gene.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Ligands of mammalian LXR and FXR that upregulate mammalian ABCC genes also induce ABCC9A in sea urchin.
“However, ligands of mammalian LXR and FXR that have been shown to upregulate mammalian ABCC (MRP) genes (Kast et al., 2002;Kullak-Ublick and Becker, 2003) also induce ABCC9A in sea urchin (Hamdoun et al., unpublished data).”
From The chemical defensome: Environmental sensing and response genes in the Strongylocentrotus purpuratus genome (2006) · cites this paper as Kast et al., 2002
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diatchenko, L. B., Lau, Y. C., Campbell, A. P., Chenchik, A. A., Moqadam, F., Huang, B. C. B., Lukyanov, S., Lukyanov, K. A., Gurskaya, N. G., Sverdlov, E. D., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.12.6025 · Cited by 3,009 · see citing works
Identification of a nuclear receptor for bile acids
Makishima, M., Okamoto, A. Y., Repa, J. J., Tu, H., Learned, R. M., Luk, A., Hull, M. V., Lustig, K. D., Mangelsdorf, D. J., & Shan, B. (1999) · Science · doi:10.1126/science.284.5418.1362 · Cited by 2,714 · see citing works
Bile Acids: Natural Ligands for an Orphan Nuclear Receptor
Parks, D. J., Blanchard, S. G., Bledsoe, R. K., Chandra, G., Consler, T. G., Kliewer, S. A., Stimmel, J. B., Willson, T. M., Zavacki, A. M., Moore, D. D., et al. (1999) · Science · doi:10.1126/science.284.5418.1365 · Cited by 2,274 · see citing works
Self-citationA regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis
Goodwin, B., Jones, S. A., Price, R. R., Watson, M. A., McKee, D. D., Moore, L. B., Galardi, C., Wilson, J. G., Lewis, M. C., Roth, M. E., et al. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00051-4 · Cited by 1,940 · see citing works
Self-citationTargeted Disruption of the Nuclear Receptor FXR/BAR Impairs Bile Acid and Lipid Homeostasis
Sinal, C. J., Tohkin, M., Miyata, M., Ward, J. M., Lambert, G., & Gonzalez, F. J. (2000) · Cell · doi:10.1016/s0092-8674(00)00062-3 · Cited by 1,819 · see citing works
Endogenous Bile Acids Are Ligands for the Nuclear Receptor FXR/BAR
Wang, H., Chen, J., Hollister, K., Sowers, L. C., & Forman, B. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80348-2 · Cited by 1,636 · see citing works
Lehmann, J., McKee, D. D., Watson, M. A., Willson, T. M., Moore, J. T., & Kliewer, S. A. (1998) · Journal of Clinical Investigation · doi:10.1172/jci3703 · Cited by 1,577 · see citing works
Self-citationAn Orphan Nuclear Receptor Activated by Pregnanes Defines a Novel Steroid Signaling Pathway
Kliewer, S. A., Moore, J. T., Wade, L., Staudinger, J. L., Watson, M. A., Jones, S. A., McKee, D. D., Oliver, B. B., Willson, T. M., Zetterström, R. H., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)80900-9 · Cited by 1,534 · see citing works
Self-citationMolecular Basis for Feedback Regulation of Bile Acid Synthesis by Nuclear Receptors
Lu, T. T., Makishima, M., Repa, J. J., Schoonjans, K., Kerr, T. A., Auwerx, J., & Mangelsdorf, D. J. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00050-2 · Cited by 1,487 · see citing works
The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity
Staudinger, J. L., Goodwin, B. J., Jones, S. A., Hawkins‐Brown, D., MacKenzie, K. I., Latour, A. M., Liu, Y., Klaassen, C. D., Brown, K. K., Reinhard, J. F., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051551698 · Cited by 1,378 · see citing works
Self-citationIdentification of a nuclear receptor that is activated by farnesol metabolites
Forman, B. M., Goode, E., Chen, J., Oro, A. E., Bradley, D. J., Perlmann, T., Noonan, D. J., Burka, L. T., McMorris, T., Lamph, W. W., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90530-8 · Cited by 1,210 · see citing works
St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor
Moore, L. B., Goodwin, B. J., Jones, S. A., Wisely, G. B., Serabjit‐Singh, C. J., Willson, T. M., Collins, J. L., & Kliewer, S. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130155097 · Cited by 946 · see citing works
Self-citationSXR, a novel steroid and xenobioticsensing nuclear receptorPreprint
Blumberg, B., Sabbagh, W., Juguilon, H., Bolado, J., van Meter, C. M., Ong, E. S., & Evans, R. M. (1998) · Genes & Development · doi:10.1101/gad.12.20.3195 · Cited by 912 · see citing works
Identification of a human nuclear receptor defines a new signaling pathway for CYP 3 A induction
Bertilsson, G., Heidrich, J., Svensson, K., Åsman, M., Jendeberg, L., Sydow‐Báckman, M., OHLSSON, R. I., Postlind, H., Blomquist, P., & Berkenstam, A. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.21.12208 · Cited by 873 · see citing works
Nuclear Receptor Response Elements Mediate Induction of Intestinal MDR1 by Rifampin
Geick, A., Eichelbaum, M. F., & Burk, O. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010173200 · Cited by 845 · see citing works
Russell, D. W., & Setchell, K. D. R. (1992) · Biochemistry · doi:10.1021/bi00135a001 · Cited by 819 · see citing works
Moore, L. B., Parks, D. J., Jones, S. A., Bledsoe, R. K., Consler, T. G., Stimmel, J. B., Goodwin, B. J., Liddle, C., Blanchard, S. G., Willson, T. M., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001215200 · Cited by 818 · see citing works
Self-citationCongenital Jaundice in Rats with a Mutation in a Multidrug Resistance-Associated Protein Gene
Paulusma, C. C., Bosma, P. J., Zaman, G. J. R., Bakker, C., Otter, M. Y., Scheffer, G. L., Scheper, R. J., Borst, P., & Elferink, R. P. J. O. (1996) · Science · doi:10.1126/science.271.5252.1126 · Cited by 817 · see citing works
Ananthanarayanan, M., Balasubramanian, N., Makishima, M., Mangelsdorf, D. J., & Suchy, F. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011610200 · Cited by 804 · see citing works
König, J., Nies, A. T., Cui, Y., Leier, I., & KEPPLER, D. O. R. (1999) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(99)00169-8 · Cited by 786 · see citing works
An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids
Xie, W., Radominska-p, A., Shi, Y., Simon, C. M., Nelson, M. C., Ong, E. S., Waxman, D. J., & Evans, R. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051014398 · Cited by 751 · see citing works
Honkakoski, P., Zelko, I. N., Sueyoshi, T., & Negishi, M. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.10.5652 · Cited by 701 · see citing works
Cui, Y., König, J., Buchholz, U., Spring, H., Leier, I., & KEPPLER, D. O. R. (1999) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)23190-4 · Cited by 674 · see citing works
The Pregnane X Receptor: A Promiscuous Xenobiotic Receptor That Has Diverged during Evolution
Jones, S. A., Moore, L. B., Shenk, J. L., Wisely, G. B., Hamilton, G. A., McKee, D. D., Tomkinson, N. C. O., LeCluyse, E. L., Lambert, M. H., Willson, T. M., et al. (2000) · Molecular Endocrinology · doi:10.1210/mend.14.1.0409 · Cited by 672 · see citing works
Self-citationThe Repressed Nuclear Receptor CAR Responds to Phenobarbital in Activating the Human CYP2B6 Gene
Sueyoshi, T., Kawamoto, T., Zelko, I. N., Honkakoski, P., & Negishi, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.10.6043 · Cited by 659 · see citing works
The nuclear receptor CAR mediates specific xenobiotic induction of drug metabolism
Wei, P., Zhang, J., Egan-Hafley, M., Liang, S., & Moore, D. D. (2000) · Nature · doi:10.1038/35038112 · Cited by 654 · see citing works
Goodwin, B. J., Hodgson, E., & Liddle, C. (1999) · Molecular Pharmacology · doi:10.1124/mol.56.6.1329 · Cited by 648 · see citing works
Self-citationBüchler, M. W., König, J., Brom, M., Kartenbeck, J., Spring, H., Horie, T., & KEPPLER, D. O. R. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.25.15091 · Cited by 639 · see citing works
Evers, R., Kool, M., van Deemter, L., Janssen, H., Calafat, J., Oomen, L. C. J. M., Paulusma, C. C., Elferink, R. P. J. O., Baas, F., Schinkel, A. H., et al. (1998) · Journal of Clinical Investigation · doi:10.1172/jci119886 · Cited by 623 · see citing works
Phenobarbital-Responsive Nuclear Translocation of the Receptor CAR in Induction of theCYP2BGene
Kawamoto, T., Sueyoshi, T., Zelko, I. N., Moore, R., Washburn, K. A., & Negishi, M. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.9.6318 · Cited by 549 · see citing works
Identification of a Chemical Tool for the Orphan Nuclear Receptor FXR
Maloney, P., Parks, D. J., Haffner, C. D., Fivush, A. M., Chandra, G., Plunket, K. D., Creech, K. L., Moore, L. B., Wilson, J. G., Lewis, M. C., et al. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm0002127 · Cited by 536 · see citing works
Self-citationReciprocal activation of Xenobiotic response genes by nuclear receptors SXR/PXR and CARPreprint
Xie, W., Barwick, J. L., Simon, C. M., Pierce, A. M., Safe, S. H., Blumberg, B., Guzelian, P. S., & Evans, R. M. (2000) · Genes & Development · doi:10.1101/gad.846800 · Cited by 510 · see citing works
Orphan Nuclear Receptors: Shifting Endocrinology into Reverse
Kliewer, S. A., Lehmann, J. M., & Willson, T. M. (1999) · Science · doi:10.1126/science.284.5415.757 · Cited by 499 · see citing works
Self-citationBaes, M. I., Gulick, T., Choi, H.-S., Martinoli, M., Simha, D., & Moore, D. D. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1544 · Cited by 492 · see citing works
Androstane metabolites bind to and deactivate the nuclear receptor CAR-β
FORMAN, B. M., Tzameli, I., Choi, H., Chen, J., Simha, D., Seol, W., Evans, R. M., & Moore, D. D. (1998) · Nature · doi:10.1038/26996 · Cited by 476 · see citing works
Schuetz, E. G., Strom, S. C., Yasuda, K., Lecureur, V., Assem, M., Brimer, C., Lamba, J. K., Kim, R. B., Ramachandran, V., Komoroski, B. J., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106340200 · Cited by 395 · see citing works
Isolation of a multispecific organic anion and cardiac glycoside transporter from rat brain
Noé, B., Hagenbuch, B., Stieger, B., & Meier, P. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.19.10346 · Cited by 392 · see citing works
Regulation of the Human CYP2B6 Gene by the Nuclear Pregnane X Receptor
Goodwin, B. J., Moore, L. B., Stoltz, C. M., McKee, D. D., & Kliewer, S. A. (2001) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)12603-x · Cited by 375 · see citing works
Self-citationSynthesis and Structure-Activity Relationships of Novel Retinoid X Receptor-Selective Retinoids
Boehm, M. F., Zhang, L., Badea, B. A., White, S. K., Mais, D. E., Berger, E. M., Suto, C. M., Goldman, M. E., & Heyman, R. A. (1994) · Journal of Medicinal Chemistry · doi:10.1021/jm00044a014 · Cited by 373 · see citing works
Phenobarbital Response Elements of Cytochrome P450 Genes and Nuclear Receptors
Sueyoshi, T., & Negishi, M. (2001) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.123 · Cited by 362 · see citing works
Identification of a Bile Acid-responsive Element in the Human Ileal Bile Acid-binding Protein Gene
Grober, J., Zaghini, I., Fujii, H., Jones, S. A., Kliewer, S. A., Willson, T. M., Ono, T., & Besnard, P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.42.29749 · Cited by 353 · see citing works
Self-citationKast-Woelbern, H. R., Nguyen, C., Sinal, C. J., Jones, S. A., Laffitte, B. A., Reue, K., Gonzalez, F. J., Willson, T. M., & Edwards, P. A. (2001) · Molecular Endocrinology · doi:10.1210/mend.15.10.0712 · Cited by 337 · see citing works
Self-citationThe Effect of Rifampin Treatment on Intestinal Expression of Human MRP Transporters
Fromm, M. F., Kauffmann, H.-M., Fritz, P., Burk, O., Kroemer, H. K., Warzok, R., Eichelbaum, M. F., Siegmund, W., & Schrenk, D. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64794-3 · Cited by 277 · see citing works
Laffitte, B. A., Kast-Woelbern, H. R., Nguyen, C., Zavacki, A. M., Moore, D. D., & Edwards, P. A. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10638 · Cited by 275 · see citing works
Self-citationUrizar, N. L., Dowhan, D. H., & Moore, D. D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007998200 · Cited by 238 · see citing works
Localization and function of the organic anion–transporting polypeptide Oatp2 in rat liver
Reichel, C., Gao, B., van Montfoort, J. E., Cattori, V., Rahner, C., Hagenbuch, B., Stieger, B., Kamisako, T., & Meier, P. J. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70463-4 · Cited by 210 · see citing works
Peptide Mimetic HIV Protease Inhibitors Are Ligands for the Orphan Receptor SXR
Dussault, I., Lin, M., Hollister, K., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100375200 · Cited by 190 · see citing works
Use of the nuclear receptor PXR to predict drug interactions
Moore, J. T., & Kliewer, S. A. (2000) · Toxicology · doi:10.1016/s0300-483x(00)00300-0 · Cited by 189 · see citing works
Self-citationHonkakoski, P., Moore, R., Washburn, K. A., & Negishi, M. (1998) · Molecular Pharmacology · doi:10.1124/mol.53.4.597 · Cited by 162 · see citing works
Kawabe, T., Chen, Z., Wada, M., et al. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00979-5 · Cited by 159 · see citing works
Models for Assessing Drug Absorption and Metabolism
Borchardt, R. T., Smith, P. L., & Wilson, G. (1996) · Pharmaceutical biotechnology · doi:10.1007/978-1-4899-1863-5 · Cited by 158 · see citing works
LeCluyse, E. L., Bullock, P. L., Parkinson, A., & Hochman, J. H. (1996) · Pharmaceutical biotechnology · doi:10.1007/978-1-4899-1863-5_9 · Cited by 134 · see citing works
Bremmelgaard, A., & Sjövall, J. (1980) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)34768-4 · Cited by 129 · see citing works
Up-regulation of transporters of the MRP family by drugs and toxins
Schrenk, D., Baus, P. R., Ermel, N., Klein, C., Vorderstemann, B., & Kauffmann, H.-M. (2001) · Toxicology Letters · doi:10.1016/s0378-4274(01)00306-x · Cited by 125 · see citing works
Dexamethasone modulation of multidrug transporters in normal tissues
Demeule, M., Jodoin, J., Beaulieu, É., et al. (1999) · FEBS Letters · doi:10.1016/s0014-5793(98)01663-9 · Cited by 124 · see citing works
Paulusma, C. C., & Elferink, R. P. J. O. (1997) · Journal of Molecular Medicine · doi:10.1007/s001090050127 · Cited by 111 · see citing works
Orphan Receptor Promiscuity in the Induction of Cytochromes P450 by Xenobiotics
Smirlis, D., Muangmoonchai, R., Edwards, M., Phillips, I. R., & Shephard, E. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m005930200 · Cited by 108 · see citing works
Two 7α‐hydroxylase enzymes in bile acid biosynthesis
Schwarz, M., Lund, E. G., & Russell, D. W. (1998) · Current Opinion in Lipidology · doi:10.1097/00041433-199804000-00006 · Cited by 103 · see citing works
Courtois, A., Payen, L. F., Guillouzo, A., & Fardel, O. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01295-8 · Cited by 100 · see citing works
Kauffmann, H.-M., & Schrenk, D. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8340 · Cited by 94 · see citing works
Kauffmann, H.-M., KEPPLER, D. O. R., Gant, T. W., & Schrenk, D. (1998) · Archives of Toxicology · doi:10.1007/s002040050571 · Cited by 71 · see citing works
Bile Acid Metabolism and the Pathophysiology of Cholestasis
Radominska, A., Treat, S., & Little, J. M. (1993) · Seminars in Liver Disease · doi:10.1055/s-2007-1007351 · Cited by 54 · see citing works
Furster, C., & Wikvall, K. (1999) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/s0005-2760(98)00175-1 · Cited by 46 · see citing works
Flagged first, then by citations
Research works printed but not linked: 6
- Staudinger, J. L., Goodwin, B., Jones, S. A., Hawkins-Brown, D., MacKenzie, K. I., LaTour, A., Liu, Y., Klassen, C. D., Brown, K. K., Reinhard, J., Willson, T. M., Koller, B. H., and Kliewer, S. A. (2001) Proc. Natl. Acad. Sci.
- Xie, W., Radominska-Pandya, A., Shi, Y., Simon, C., Nelson, M. C., Ong, E. S., Waxman, D. J., and Evans, R. M. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 3375-3380
- Bertilsson, G., Heidrich, J., Svensson, K., Asman, M., Jendeberg, L., Sydow- Ba ¨ckman, M., Ohlsson, R., Postlind, H., Blomquist, P., and Berkenstam, A. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 12208 -12213
- Noe ´, B., Hagenbuch, B., Stieger, B., and Meier, P. J. (1997) Proc. Natl. Acad. Sci. U. S. A. 94, 10346 -10350
- Diatchenko, L., Lau, Y. F., Campbell, A. P., Chenchik, A., Moqadam, F., Huang, B., Lukyanov, S., Lukyanov, K., Gurskaya, N., Sverdlov, E. D., and Siebert, P. D. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 6025-6030
- Moore, L. B., Goodwin, B., Jones, S. A., Wisely, G. B., Serabjit-Singh, C. J., Willson, T. M., Collins, J. L., and Kliewer, S. A. (2000) Proc. Natl. Acad. Sci.
Cited by
Sorted by citations
Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009) · Physiological Reviews · doi:10.1152/physrev.00010.2008 · Cited by 1,678 · see citing works
Khovidhunkit, W., Kim, M.-S., Memon, R. A., Shigenaga, J. K., Moser, A. H., Feingold, K. R., & Grunfeld, C. (2004) · Journal of Lipid Research · doi:10.1194/jlr.r300019-jlr200 · Cited by 1,481 · see citing works
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280 · see citing works
Bile salt transporters: molecular characterization, function, and regulation
Trauner, M., & Boyer, J. L. (2003) · Physiological Reviews · doi:10.1152/physrev.00027.2002 · Cited by 999 · see citing works
Bile acid signaling in metabolic disease and drug therapy
Li, T., & Chiang, J. Y. L. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008201 · Cited by 935 · see citing works
Bile acid receptors as targets for drug development
Schaap, F. G., Trauner, M., & Jansen, P. L. M. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.151 · Cited by 696 · see citing works
New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond
Beuers, U., Trauner, M., Jansen, P., & Poupon, R. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.023 · Cited by 537 · see citing works
Fiorucci, S., Antonelli, E., Rizzo, G., Renga, B., Mencarelli, A., Riccardi, L., Orlandi, S., Pellicciari, R., & Morelli, A. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.08.001 · Cited by 472 · see citing works
Molecular physiology of bile acid signaling in health, disease, and aging
Perino, A., Demagny, H., Velazquez-Villegas, L., & Schoonjans, K. (2021) · Physiological Reviews · doi:10.1152/physrev.00049.2019 · Cited by 481 · see citing works
FXR: a metabolic regulator and cell protector
Wang, Y.-D., Chen, W.-D., Moore, D. D., & Huang, W. (2008) · Cell Research · doi:10.1038/cr.2008.289 · Cited by 389 · see citing works
FXR, a multipurpose nuclear receptor
Lee, F. Y., Lee, H., Hubbert, M. L., Edwards, P. A., & Zhang, Y. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.08.002 · Cited by 344 · see citing works
Self-citationPrimary biliary cholangitis: pathogenesis and therapeutic opportunities
Gulamhusein, A. F., & Hirschfield, G. M. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0226-7 · Cited by 308 · see citing works
Goldstone, J. V., Hamdoun, A., Cole, B. J., Howard-Ashby, M., Nebert, D. W., Scally, M., Dean, M., Epel, D., Hahn, M. E., & Stegeman, J. J. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.08.066 · Cited by 280 · see citing works
Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects
di Masi, A., Marinis, E. D., Ascenzi, P., & Marino, M. (2009) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2009.04.002 · Cited by 288 · see citing works
Coordinate transcriptional regulation of bile acid homeostasis and drug metabolism
Eloranta, J. J., & Kullak-Ublick, G. A. (2005) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2004.09.019 · Cited by 260 · see citing works
Shah, Y. M., Ma, X., Morimura, K., Kim, I., & Gonzalez, F. J. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00528.2006 · Cited by 231 · see citing works
Honda, A., Ikegami, T., Nakamuta, M., Miyazaki, T., Iwamoto, J., Hirayama, T., Saito, Y., Takikawa, H., Imawari, M., & Matsuzaki, Y. (2013) · Hepatology · doi:10.1002/hep.26018 · Cited by 210 · see citing works
The biosynthesis, signaling, and neurological functions of bile acids
Kiriyama, Y., & Nochi, H. (2019) · Biomolecules · doi:10.3390/biom9060232 · Cited by 204 · see citing works
Prieur, X., Coste, H., & Rodríguez, J. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301302200 · Cited by 194 · see citing works
Molecular basis of bile acid-FXR-FGF15/19 signaling axis
Katafuchi, T., & Makishima, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116046 · Cited by 193 · see citing works
Identification of Farnesoid X Receptor β as a Novel Mammalian Nuclear Receptor Sensing Lanosterol
Otte, K., Kranz, H., Kober, I., Thompson, P., Hoefer, M., Haubold, B., Remmel, B., Voss, H., Kaiser, C., Albers, M., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.3.864-872.2003 · Cited by 176 · see citing works
Nuclear receptors in bile acid metabolism
Li, T., & Chiang, J. Y. L. (2013) · Drug Metabolism Reviews · doi:10.3109/03602532.2012.740048 · Cited by 176 · see citing works
Nuclear receptors as therapeutic targets in cholestatic liver diseases
Zollner, G., & Trauner, M. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2008.00030.x · Cited by 146 · see citing works
Nonsteroidal FXR Ligands: Current Status and Clinical Applications
Gege, C., Hambruch, E., Hambruch, N., Kinzel, O., & Kremoser, C. (2019) · Handbook of Experimental Pharmacology · doi:10.1007/164_2019_232 · Cited by 83 · see citing works
Geier, A., Dietrich, C. G., Grote, T., Beuers, U., Prüfer, T., Fraunberger, P., Matern, S., Gartung, C., Gerbes, A. L., & Bilzer, M. (2005) · Journal of Hepatology · doi:10.1016/j.jhep.2005.05.031 · Cited by 66 · see citing works
Shoda, J., Inada, Y., Tsuji, A., Kusama, H., Ueda, T., Ikegami, T., Suzuki, H., Sugiyama, Y., Cohen, D. E., & Tanaka, N. (2004) · Journal of Lipid Research · doi:10.1194/jlr.m400132-jlr200 · Cited by 58 · see citing works
- Authors
- Kast, H. R., Goodwin, B., Tarr, P. T., Jones, S. A., Anisfeld, A. M., Stoltz, C. M., Tontonoz, P., Kliewer, S., Willson, T. M., & Edwards, P. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- GlaxoSmithKline (United States) (US)
- Corresponding author
- Edwards, Peter A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 277
- Issue
- 4
- Pages
- 2908-2915
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2125457175
- Cited by
- 916
- References
- 63
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 11 · 2023: 23 · 2022: 31 · 2021: 21 · 2020: 22 · 2019: 27 · 2018: 22 · 2017: 21 · 2016: 23 · 2015: 20 · 2014: 33 · 2013: 43 · 2012: 44
- FWCI
- 35.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Education
- American Heart Association
- National Institutes of Health (HL30568)
- National Heart, Lung, and Blood Institute (HL3 0568, HL 68445, P01HL030568, R01HL068445)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- MRP2, pregnane X receptor, constitutive androstane receptor, nuclear receptor regulation, gene expression regulation, hepatocytes, retinoid X receptor alpha, chenodeoxycholic acid, GW4064, phenobarbital
- MeSH terms
- Pregnane X Receptor, Multidrug Resistance-Associated Protein 2, Constitutive Androstane Receptor, Receptor, Farnesoid X-Activated, Animals, Base Sequence, Bile Acids and Salts, Cell Line, Cell Nucleus, Cells, Cultured, DNA-Binding Proteins, Humans, Isoxazoles, Ligands, Liver, Models, Biological, Molecular Sequence Data, Nucleic Acid Hybridization, Phenobarbital, Promoter Regions, Genetic, Protein Binding, Receptors, Steroid, RNA, Messenger, Transcription Factors, Transcription, Genetic, Blotting, Northern, Signal Transduction, Transcriptional Activation, Genes, Reporter, Receptors, Cytoplasmic and Nuclear, Drug Resistance, Multiple, Protein Transport, Hepatocytes, Membrane Transport Proteins, ATP-Binding Cassette, Sub-Family C Proteins, Mice, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
