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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Review Article

Dual Role of Pregnane X Receptor in Nonalcoholic Fatty Liver Disease

Author(s): Yuan Xu, Ziming An, Shufei Wang, Yiming Ni, Mingmei Zhou*, Qin Feng*, Xiaojun Gou*, Meiling Xu and Ying Qi

Volume 17, 2024

Published on: 13 October, 2023

Article ID: e18761429259143 Pages: 17

DOI: 10.2174/0118761429259143230927110556

Price: $65

Abstract

The incidence of nonalcoholic fatty liver disease (NAFLD) has been rising worldwide in parallel with diabetes and metabolic syndrome. NAFLD refers to a spectrum of liver abnormalities with a variable course, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), eventually leading to cirrhosis and hepatocellular carcinoma. Pregnane X receptor (PXR), a member of the nuclear receptor superfamily, plays a prominent part in the regulation of endogenous metabolic genes in NAFLD. Recent studies have suggested that PXR has therapeutic potential for NAFLD, yet the relationship between PXR and NAFLD remains controversial. In this review, PXR is proposed to play a dual role in the development and progression of NAFLD. Its activation will aggravate steatosis of the liver, reduce inflammatory response, and prevent liver fibrosis. In addition, the interactions between PXR, substance metabolism, inflammation, fibrosis, and gut microbiota in non-alcoholic fatty liver were elucidated. Due to limited therapeutic options, a better understanding of the contribution of PXR to the pathogenesis of NAFLD should facilitate the design of innovative drugs targeting NAFLD.

[1]
Eslam, M.; Sanyal, A.J.; George, J.; Sanyal, A.; Neuschwander-Tetri, B.; Tiribelli, C.; Kleiner, D.E.; Brunt, E.; Bugianesi, E.; Yki-Järvinen, H.; Grønbæk, H.; Cortez-Pinto, H.; George, J.; Fan, J.; Valenti, L.; Abdelmalek, M.; Romero-Gomez, M.; Rinella, M.; Arrese, M.; Eslam, M.; Bedossa, P.; Newsome, P.N.; Anstee, Q.M.; Jalan, R.; Bataller, R.; Loomba, R.; Sookoian, S.; Sarin, S.K.; Harrison, S.; Kawaguchi, T.; Wong, V.W-S.; Ratziu, V.; Yilmaz, Y.; Younossi, Z. MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology, 2020, 158(7), 1999-2014.e1.
[http://dx.doi.org/10.1053/j.gastro.2019.11.312] [PMID: 32044314]
[2]
Angulo, P.; Kleiner, D.E.; Dam-Larsen, S.; Adams, L.A.; Bjornsson, E.S.; Charatcharoenwitthaya, P.; Mills, P.R.; Keach, J.C.; Lafferty, H.D.; Stahler, A.; Haflidadottir, S.; Bendtsen, F. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology, 2015, 149(2), 389-397.e10.
[http://dx.doi.org/10.1053/j.gastro.2015.04.043] [PMID: 25935633]
[3]
Ekstedt, M.; Hagström, H.; Nasr, P.; Fredrikson, M.; Stål, P.; Kechagias, S.; Hultcrantz, R. Fibrosis stage is the strongest predictor for disease‐specific mortality in NAFLD after up to 33 years of follow‐up. Hepatology, 2015, 61(5), 1547-1554.
[http://dx.doi.org/10.1002/hep.27368] [PMID: 25125077]
[4]
Pais, R.; Barritt, A.S., IV; Calmus, Y.; Scatton, O.; Runge, T.; Lebray, P.; Poynard, T.; Ratziu, V.; Conti, F. NAFLD and liver transplantation: Current burden and expected challenges. J. Hepatol., 2016, 65(6), 1245-1257.
[http://dx.doi.org/10.1016/j.jhep.2016.07.033] [PMID: 27486010]
[5]
Saiman, Y.; Hooks, R.; Carr, R.M. High-risk groups for non-alcoholic fatty liver and non-alcoholic steatohepatitis development and progression. Curr. Hepatol. Rep., 2020, 19(4), 412-419.
[http://dx.doi.org/10.1007/s11901-020-00539-5]
[6]
Luo, W.; Xin, Y.; Zhao, X.; Zhang, F.; Liu, C.; Fan, H.; Xi, T.; Xiong, J. Suppression of carboxylesterases by imatinib mediated by the down-regulation of pregnane X receptor. Br. J. Pharmacol., 2017, 174(8), 700-717.
[http://dx.doi.org/10.1111/bph.13731] [PMID: 28128444]
[7]
Petryszak, R.; Keays, M.; Tang, Y.A.; Fonseca, N.A.; Barrera, E.; Burdett, T.; Füllgrabe, A.; Fuentes, A.M.P.; Jupp, S.; Koskinen, S.; Mannion, O.; Huerta, L.; Megy, K.; Snow, C.; Williams, E.; Barzine, M.; Hastings, E.; Weisser, H.; Wright, J.; Jaiswal, P.; Huber, W.; Choudhary, J.; Parkinson, H.E.; Brazma, A. Expression atlas update—an integrated database of gene and protein expression in humans, animals and plants. Nucleic Acids Res., 2016, 44(D1), D746-D752.
[http://dx.doi.org/10.1093/nar/gkv1045] [PMID: 26481351]
[8]
Byrne, C.D.; Targher, G. NAFLD: A multisystem disease. J. Hepatol., 2015, 62(1)(Suppl.), S47-S64.
[http://dx.doi.org/10.1016/j.jhep.2014.12.012] [PMID: 25920090]
[9]
Targher, G.; Byrne, C.D.; Lonardo, A.; Zoppini, G.; Barbui, C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. J. Hepatol., 2016, 65(3), 589-600.
[http://dx.doi.org/10.1016/j.jhep.2016.05.013] [PMID: 27212244]
[10]
Cotter, T.G.; Rinella, M. Nonalcoholic fatty liver disease 2020: The state of the disease. Gastroenterology, 2020, 158(7), 1851-1864.
[http://dx.doi.org/10.1053/j.gastro.2020.01.052] [PMID: 32061595]
[11]
Oladimeji, P.O.; Chen, T. PXR: More than just a master xenobiotic receptor. Mol. Pharmacol., 2018, 93(2), 119-127.
[http://dx.doi.org/10.1124/mol.117.110155] [PMID: 29113993]
[12]
Puengel, T.; Liu, H.; Guillot, A.; Heymann, F.; Tacke, F.; Peiseler, M. Nuclear receptors linking metabolism, inflammation, and fibrosis in nonalcoholic fatty liver disease. Int. J. Mol. Sci., 2022, 23(5), 2668.
[http://dx.doi.org/10.3390/ijms23052668] [PMID: 35269812]
[13]
Romero, F.A.; Jones, C.T.; Xu, Y.; Fenaux, M.; Halcomb, R.L. The race to bash NASH: Emerging targets and drug development in a complex liver disease. J. Med. Chem., 2020, 63(10), 5031-5073.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01701] [PMID: 31930920]
[14]
Furuta, K.; Guo, Q.; Pavelko, K.D.; Lee, J.H.; Robertson, K.D.; Nakao, Y.; Melek, J.; Shah, V.H.; Hirsova, P.; Ibrahim, S.H. Lipid-induced endothelial vascular cell adhesion molecule 1 promotes nonalcoholic steatohepatitis pathogenesis. J. Clin. Invest., 2021, 131(6), e143690.
[http://dx.doi.org/10.1172/JCI143690] [PMID: 33476308]
[15]
Pondugula, S.R.; Mani, S. Pregnane xenobiotic receptor in cancer pathogenesis and therapeutic response. Cancer Lett., 2013, 328(1), 1-9.
[http://dx.doi.org/10.1016/j.canlet.2012.08.030] [PMID: 22939994]
[16]
Liang, Y.; Gong, Y.; Jiang, Q.; Yu, Y.; Zhang, J. Environmental endocrine disruptors and pregnane X receptor action: A review. Food Chem. Toxicol., 2023, 179, 113976.
[http://dx.doi.org/10.1016/j.fct.2023.113976] [PMID: 37532173]
[17]
Ming, W.; Luan, Z.; Yao, Y.; Liu, H.; Hu, S.; Du, C.; Zhang, C.; Zhao, Y.; Huang, Y.; Sun, X.; Qiao, R.; Xu, H.; Guan, Y.; Zhang, X. Pregnane X receptor activation alleviates renal fibrosis in mice via interacting with p53 and inhibiting the Wnt7a/β-catenin signaling. Acta Pharmacol. Sin., 2023, 44(10), 2015-90.
[http://dx.doi.org/10.1038/s41401-023-01113-7] [PMID: 37344564]
[18]
Xing, Y.; Yan, J.; Niu, Y. PXR: A center of transcriptional regulation in cancer. Acta Pharm. Sin. B, 2020, 10(2), 197-206.
[http://dx.doi.org/10.1016/j.apsb.2019.06.012] [PMID: 32082968]
[19]
Fan, S.; Yan, Y.; Xia, Y.; Zhou, Z.; Luo, L.; Zhu, M.; Han, Y.; Yao, D.; Zhang, L.; Fang, M.; Peng, L.; Yu, J.; Liu, Y.; Gao, X.; Guan, H.; Li, H.; Wang, C.; Wu, X.; Zhu, H.; Cao, Y.; Huang, C. Pregnane X receptor agonist nomilin extends lifespan and healthspan in preclinical models through detoxification functions. Nat. Commun., 2023, 14(1), 3368.
[http://dx.doi.org/10.1038/s41467-023-39118-9] [PMID: 37291126]
[20]
Lv, Y.; Luo, Y.Y.; Ren, H.W.; Li, C.J.; Xiang, Z.X.; Luan, Z.L. The role of pregnane X receptor (PXR) in substance metabolism. Front. Endocrinol., 2022, 13, 959902.
[http://dx.doi.org/10.3389/fendo.2022.959902] [PMID: 36111293]
[21]
Sun, L.; Sun, Z.; Wang, Q.; Zhang, Y.; Jia, Z. Role of nuclear receptor PXR in immune cells and inflammatory diseases. Front. Immunol., 2022, 13, 969399.
[http://dx.doi.org/10.3389/fimmu.2022.969399] [PMID: 36119030]
[22]
Bautista-Olivier, C.D.; Elizondo, G. PXR as the tipping point between innate immune response, microbial infections, and drug metabolism. Biochem. Pharmacol., 2022, 202, 115147.
[http://dx.doi.org/10.1016/j.bcp.2022.115147] [PMID: 35714683]
[23]
Wahlang, B.; Falkner, K.C.; Gregory, B.; Ansert, D.; Young, D.; Conklin, D.J.; Bhatnagar, A.; McClain, C.J.; Cave, M. Polychlorinated biphenyl 153 is a diet-dependent obesogen that worsens nonalcoholic fatty liver disease in male C57BL6/J mice. J. Nutr. Biochem., 2013, 24(9), 1587-1595.
[http://dx.doi.org/10.1016/j.jnutbio.2013.01.009] [PMID: 23618531]
[24]
Kim, S.; Choi, S.; Dutta, M.; Asubonteng, J.O.; Polunas, M.; Goedken, M.; Gonzalez, F.J.; Cui, J.Y.; Gyamfi, M.A. Pregnane X receptor exacerbates nonalcoholic fatty liver disease accompanied by obesity- and inflammation-prone gut microbiome signature. Biochem. Pharmacol., 2021, 193, 114698.
[http://dx.doi.org/10.1016/j.bcp.2021.114698] [PMID: 34303710]
[25]
Saraswathi, V.; Perriotte-Olson, C.; Ganesan, M.; Desouza, C.V.; Alnouti, Y.; Duryee, M.J.; Thiele, G.M.; Nordgren, T.M.; Clemens, D.L. A combination of dietary N-3 fatty acids and a cyclooxygenase-1 inhibitor attenuates nonalcoholic fatty liver disease in mice. J. Nutr. Biochem., 2017, 42, 149-159.
[http://dx.doi.org/10.1016/j.jnutbio.2017.01.011] [PMID: 28187366]
[26]
Kong, L.; An, X.; Hu, L.; Zhang, S.; Liu, L.; Zhao, S.; Wang, R.; Nan, Y. Resveratrol ameliorates nutritional steatohepatitis through the mmu‑miR‑599/PXR pathway. Int. J. Mol. Med., 2022, 49(4), 47.
[http://dx.doi.org/10.3892/ijmm.2022.5102] [PMID: 35137921]
[27]
Carnahan, V.; Redinbo, M. Structure and function of the human nuclear xenobiotic receptor PXR. Curr. Drug Metab., 2005, 6(4), 357-367.
[http://dx.doi.org/10.2174/1389200054633844] [PMID: 16101574]
[28]
Mangelsdorf, D.J.; Evans, R.M. The RXR heterodimers and orphan receptors. Cell, 1995, 83(6), 841-850.
[http://dx.doi.org/10.1016/0092-8674(95)90200-7] [PMID: 8521508]
[29]
Hou, Y.; Moreau, F.; Chadee, K. PPARγ is an E3 ligase that induces the degradation of NFκB/p65. Nat. Commun., 2012, 3(1), 1300.
[http://dx.doi.org/10.1038/ncomms2270] [PMID: 23250430]
[30]
Rana, M.; Dash, A.K.; Ponnusamy, K.; Tyagi, R.K. Nuclear localization signal region in nuclear receptor PXR governs the receptor association with mitotic chromatin. Chromosome Res., 2018, 26(4), 255-276.
[http://dx.doi.org/10.1007/s10577-018-9583-2] [PMID: 30009337]
[31]
Umesono, K.; Evans, R.M. Determinants of target gene specificity for steroid/thyroid hormone receptors. Cell, 1989, 57(7), 1139-1146.
[http://dx.doi.org/10.1016/0092-8674(89)90051-2] [PMID: 2500251]
[32]
Buchman, C.D.; Chai, S.C.; Chen, T. A current structural perspective on PXR and CAR in drug metabolism. Expert Opin. Drug Metab. Toxicol., 2018, 14(6), 635-647.
[http://dx.doi.org/10.1080/17425255.2018.1476488] [PMID: 29757018]
[33]
di Masi, A.; Marinis, E.D.; Ascenzi, P.; Marino, M. Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects. Mol. Aspects Med., 2009, 30(5), 297-343.
[http://dx.doi.org/10.1016/j.mam.2009.04.002] [PMID: 19427329]
[34]
Bourguet, W.; Germain, P.; Gronemeyer, H. Nuclear receptor ligand-binding domains: Three-dimensional structures, molecular interactions and pharmacological implications. Trends Pharmacol. Sci., 2000, 21(10), 381-388.
[http://dx.doi.org/10.1016/S0165-6147(00)01548-0] [PMID: 11050318]
[35]
Oladimeji, P.; Cui, H.; Zhang, C.; Chen, T. Regulation of PXR and CAR by protein-protein interaction and signaling crosstalk. Expert Opin. Drug Metab. Toxicol., 2016, 12(9), 997-1010.
[http://dx.doi.org/10.1080/17425255.2016.1201069] [PMID: 27295009]
[36]
Hall, A.; Chanteux, H.; Ménochet, K.; Ledecq, M.; Schulze, M.S.E.D. Designing out PXR activity on drug discovery projects: A review of structure-based methods, empirical and computational approaches. J. Med. Chem., 2021, 64(10), 6413-6522.
[http://dx.doi.org/10.1021/acs.jmedchem.0c02245] [PMID: 34003642]
[37]
Chai, S.C.; Wright, W.C.; Chen, T. Strategies for developing pregnane X receptor antagonists: Implications from metabolism to cancer. Med. Res. Rev., 2020, 40(3), 1061-1083.
[http://dx.doi.org/10.1002/med.21648] [PMID: 31782213]
[38]
Mackowiak, B.; Wang, H. Mechanisms of xenobiotic receptor activation: Direct vs. indirect. Biochim. Biophys. Acta. Gene Regul. Mech., 2016, 1859(9), 1130-1140.
[http://dx.doi.org/10.1016/j.bbagrm.2016.02.006] [PMID: 26877237]
[39]
Orans, J.; Teotico, D.G.; Redinbo, M.R. The nuclear xenobiotic receptor pregnane X receptor: Recent insights and new challenges. Mol. Endocrinol., 2005, 19(12), 2891-2900.
[http://dx.doi.org/10.1210/me.2005-0156] [PMID: 15961506]
[40]
Casabar, R.C.T.; Das, P.C.; DeKrey, G.K.; Gardiner, C.S.; Cao, Y.; Rose, R.L.; Wallace, A.D. Endosulfan induces CYP2B6 and CYP3A4 by activating the pregnane X receptor. Toxicol. Appl. Pharmacol., 2010, 245(3), 335-343.
[http://dx.doi.org/10.1016/j.taap.2010.03.017] [PMID: 20361990]
[41]
De Bosscher, K.; Desmet, S.J.; Clarisse, D.; Estébanez-Perpiña, E.; Brunsveld, L. Nuclear receptor crosstalk — defining the mechanisms for therapeutic innovation. Nat. Rev. Endocrinol., 2020, 16(7), 363-377.
[http://dx.doi.org/10.1038/s41574-020-0349-5] [PMID: 32303708]
[42]
Saini, S.P.S.; Mu, Y.; Gong, H.; Toma, D.; Uppal, H.; Ren, S.; Li, S.; Poloyac, S.M.; Xie, W. Dual role of orphan nuclear receptor pregnane X receptor in bilirubin detoxification in mice. Hepatology, 2005, 41(3), 497-505.
[http://dx.doi.org/10.1002/hep.20570] [PMID: 15726644]
[43]
Poudel, S.; Huber, A.D.; Chen, T. Regulation of nuclear receptors PXR and CAR by small molecules and signal crosstalk: Roles in drug metabolism and beyond. Drug Metab. Dispos., 2022.
[PMID: 36116789]
[44]
Bwayi, M.N.; Garcia-Maldonado, E.; Chai, S.C.; Xie, B.; Chodankar, S.; Huber, A.D.; Wu, J.; Annu, K.; Wright, W.C.; Lee, H.M.; Seetharaman, J.; Wang, J.; Buchman, C.D.; Peng, J.; Chen, T. Molecular basis of crosstalk in nuclear receptors: Heterodimerization between PXR and CAR and the implication in gene regulation. Nucleic Acids Res., 2022, 50(6), 3254-3275.
[http://dx.doi.org/10.1093/nar/gkac133] [PMID: 35212371]
[45]
Suino, K.; Peng, L.; Reynolds, R.; Li, Y.; Cha, J.Y.; Repa, J.J.; Kliewer, S.A.; Xu, H.E. The nuclear xenobiotic receptor CAR: Structural determinants of constitutive activation and heterodimerization. Mol. Cell, 2004, 16(6), 893-905.
[PMID: 15610733]
[46]
Willhite, C.C.; Ball, G.L.; McLellan, C.J. Total allowable concentrations of monomeric inorganic aluminum and hydrated aluminum silicates in drinking water. Crit. Rev. Toxicol., 2012, 42(5), 358-442.
[http://dx.doi.org/10.3109/10408444.2012.674101] [PMID: 22512666]
[47]
Kumar, S.; Jaiswal, B.; Kumar, S.; Negi, S.; Tyagi, R.K. Cross-talk between androgen receptor and pregnane and xenobiotic receptor reveals existence of a novel modulatory action of anti-androgenic drugs. Biochem. Pharmacol., 2010, 80(7), 964-976.
[http://dx.doi.org/10.1016/j.bcp.2010.06.009] [PMID: 20599793]
[48]
Cocci, P.; Mosconi, G.; Palermo, F.A. Pregnane X receptor (PXR) signaling in seabream primary hepatocytes exposed to extracts of seawater samples collected from polycyclic aromatic hydrocarbons (PAHs)-contaminated coastal areas. Mar. Environ. Res., 2017, 130, 181-186.
[http://dx.doi.org/10.1016/j.marenvres.2017.07.011] [PMID: 28760623]
[49]
Jonker, J.W.; Liddle, C.; Downes, M. FXR and PXR: Potential therapeutic targets in cholestasis. J. Steroid Biochem. Mol. Biol., 2012, 130(3-5), 147-158.
[http://dx.doi.org/10.1016/j.jsbmb.2011.06.012] [PMID: 21801835]
[50]
Skandalaki, A.; Sarantis, P.; Theocharis, S. Pregnane X receptor (PXR) polymorphisms and cancer treatment. Biomolecules, 2021, 11(8), 1142.
[http://dx.doi.org/10.3390/biom11081142] [PMID: 34439808]
[51]
Sugatani, J.; Uchida, T.; Kurosawa, M.; Yamaguchi, M.; Yamazaki, Y.; Ikari, A.; Miwa, M. Regulation of pregnane X receptor (PXR) function and UGT1A1 gene expression by posttranslational modification of PXR protein. Drug Metab. Dispos., 2012, 40(10), 2031-2040.
[http://dx.doi.org/10.1124/dmd.112.046748] [PMID: 22829544]
[52]
Pasquel, D.; Doricakova, A.; Li, H.; Kortagere, S.; Krasowski, M.D.; Biswas, A.; Walton, W.G.; Redinbo, M.R.; Dvorak, Z.; Mani, S. Acetylation of lysine 109 modulates pregnane X receptor DNA binding and transcriptional activity. Biochim. Biophys. Acta. Gene Regul. Mech., 2016, 1859(9), 1155-1169.
[http://dx.doi.org/10.1016/j.bbagrm.2016.01.006] [PMID: 26855179]
[53]
Cui, W.; Sun, M.; Zhang, S.; Shen, X.; Galeva, N.; Williams, T.D.; Staudinger, J.L. A SUMO-acetyl switch in PXR biology. Biochim. Biophys. Acta. Gene Regul. Mech., 2016, 1859(9), 1170-1182.
[http://dx.doi.org/10.1016/j.bbagrm.2016.02.008] [PMID: 26883953]
[54]
Smutny, T.; Mani, S.; Pavek, P. Post-translational and post-transcriptional modifications of pregnane X receptor (PXR) in regulation of the cytochrome P450 superfamily. Curr. Drug Metab., 2013, 14(10), 1059-1069.
[http://dx.doi.org/10.2174/1389200214666131211153307] [PMID: 24329114]
[55]
Yokobori, K.; Gruzdev, A.; Negishi, M. Mice blocking Ser347 phosphorylation of pregnane x receptor develop hepatic fasting-induced steatosis and hypertriglyceridemia. Biochem. Biophys. Res. Commun., 2022, 615, 75-80.
[http://dx.doi.org/10.1016/j.bbrc.2022.05.055] [PMID: 35609418]
[56]
Qin, M.; Xin, Y.; Bian, Y.; Yang, X.; Xi, T.; Xiong, J. Phosphorylation-induced ubiquitination and degradation of PXR through CDK2-TRIM21 axis. Cells, 2022, 11(2), 264.
[http://dx.doi.org/10.3390/cells11020264] [PMID: 35053380]
[57]
Wang, Y.M.; Chai, S.C.; Lin, W.; Chai, X.; Elias, A.; Wu, J.; Ong, S.S.; Pondugula, S.R.; Beard, J.A.; Schuetz, E.G.; Zeng, S.; Xie, W.; Chen, T. Serine 350 of human pregnane X receptor is crucial for its heterodimerization with retinoid X receptor alpha and transactivation of target genes in vitro and in vivo. Biochem. Pharmacol., 2015, 96(4), 357-368.
[http://dx.doi.org/10.1016/j.bcp.2015.06.018] [PMID: 26119819]
[58]
Bakshi, K.; Ranjitha, B.; Dubey, S.; Jagannadham, J.; Jaiswal, B.; Gupta, A. Novel complex of HAT protein TIP60 and nuclear receptor PXR promotes cell migration and adhesion. Sci. Rep., 2017, 7(1), 3635.
[http://dx.doi.org/10.1038/s41598-017-03783-w] [PMID: 28623334]
[59]
Cui, W.; Sun, M.; Galeva, N.; Williams, T.D.; Azuma, Y.; Staudinger, J.L. SUMOylation and ubiquitylation circuitry controls pregnane X receptor biology in hepatocytes. Drug Metab. Dispos., 2015, 43(9), 1316-1325.
[http://dx.doi.org/10.1124/dmd.115.065201] [PMID: 26063058]
[60]
Ekins, S.; Chang, C.; Mani, S.; Krasowski, M.D.; Reschly, E.J.; Iyer, M.; Kholodovych, V.; Ai, N.; Welsh, W.J.; Sinz, M.; Swaan, P.W.; Patel, R.; Bachmann, K. Human pregnane X receptor antagonists and agonists define molecular requirements for different binding sites. Mol. Pharmacol., 2007, 72(3), 592-603.
[http://dx.doi.org/10.1124/mol.107.038398] [PMID: 17576789]
[61]
Pavek, P. Pregnane X Receptor (PXR)-Mediated Gene Repression and Cross-Talk of PXR with Other Nuclear Receptors via Coactivator Interactions. Front. Pharmacol., 2016, 7, 456.
[http://dx.doi.org/10.3389/fphar.2016.00456] [PMID: 27932985]
[62]
Moreau, A.; Vilarem, M.J.; Maurel, P.; Pascussi, J.M. Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol. Pharm., 2008, 5(1), 35-41.
[http://dx.doi.org/10.1021/mp700103m] [PMID: 18159929]
[63]
Bhalla, S.; Ozalp, C.; Fang, S.; Xiang, L.; Kemper, J.K. Ligand-activated pregnane X receptor interferes with HNF-4 signaling by targeting a common coactivator PGC-1alpha. Functional implications in hepatic cholesterol and glucose metabolism. J. Biol. Chem., 2004, 279(43), 45139-45147.
[http://dx.doi.org/10.1074/jbc.M405423200] [PMID: 15322103]
[64]
Pondugula, S.R.; Dong, H.; Chen, T. Phosphorylation and protein–protein interactions in PXR-mediated CYP3A repression. Expert Opin. Drug Metab. Toxicol., 2009, 5(8), 861-873.
[http://dx.doi.org/10.1517/17425250903012360] [PMID: 19505191]
[65]
Krausova, L.; Stejskalova, L.; Wang, H.; Vrzal, R.; Dvorak, Z.; Mani, S.; Pavek, P. Metformin suppresses pregnane X receptor (PXR)-regulated transactivation of CYP3A4 gene. Biochem. Pharmacol., 2011, 82(11), 1771-1780.
[http://dx.doi.org/10.1016/j.bcp.2011.08.023] [PMID: 21920351]
[66]
Smutny, T.; Bitman, M.; Urban, M.; Dubecka, M.; Vrzal, R.; Dvorak, Z.; Pavek, P. U0126, a mitogen-activated protein kinase kinase 1 and 2 (MEK1 and 2) inhibitor, selectively up-regulates main isoforms of CYP3A subfamily via a pregnane X receptor (PXR) in HepG2 cells. Arch. Toxicol., 2014, 88(12), 2243-2259.
[http://dx.doi.org/10.1007/s00204-014-1254-2] [PMID: 24819614]
[67]
Li, C.W.; Dinh, G.K.; Chen, J.D. Preferential physical and functional interaction of pregnane X receptor with the SMRTalpha isoform. Mol. Pharmacol., 2009, 75(2), 363-373.
[http://dx.doi.org/10.1124/mol.108.047845] [PMID: 18978041]
[68]
Piccinin, E.; Villani, G.; Moschetta, A. Metabolic aspects in NAFLD, NASH and hepatocellular carcinoma: The role of PGC1 coactivators. Nat. Rev. Gastroenterol. Hepatol., 2019, 16(3), 160-174.
[http://dx.doi.org/10.1038/s41575-018-0089-3] [PMID: 30518830]
[69]
Shizu, R.; Ezaki, K.; Sato, T.; Sugawara, A.; Hosaka, T.; Sasaki, T.; Yoshinari, K. PXR suppresses PPARα-dependent HMGCS2 gene transcription by inhibiting the interaction between PPARα and PGC1α. Cells, 2021, 10(12), 3550.
[http://dx.doi.org/10.3390/cells10123550] [PMID: 34944058]
[70]
Staudinger, J.L.; Goodwin, B.; Jones, S.A.; Hawkins-Brown, D.; MacKenzie, K.I.; LaTour, A.; Liu, Y.; Klaassen, C.D.; Brown, K.K.; Reinhard, J.; Willson, T.M.; Koller, B.H.; Kliewer, S.A. The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc. Natl. Acad. Sci. USA, 2001, 98(6), 3369-3374.
[http://dx.doi.org/10.1073/pnas.051551698] [PMID: 11248085]
[71]
Copple, B.L.; Li, T. Pharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules. Pharmacol. Res., 2016, 104, 9-21.
[http://dx.doi.org/10.1016/j.phrs.2015.12.007] [PMID: 26706784]
[72]
Juřica, J.; Dovrtělová, G.; Nosková, K.; Zendulka, O. Bile acids, nuclear receptors and cytochrome P450. Physiol. Res., 2016, 65(Suppl. 4), S427-S440.
[http://dx.doi.org/10.33549/physiolres.933512] [PMID: 28006925]
[73]
Asif, S.; Kim, R.Y.; Fatica, T.; Sim, J.; Zhao, X.; Oh, Y.; Denoncourt, A.; Cheung, A.C.; Downey, M.; Mulvihill, E.E.; Kim, K.H. Hmgcs2-mediated ketogenesis modulates high-fat diet-induced hepatosteatosis. Mol. Metab., 2022, 61, 101494.
[http://dx.doi.org/10.1016/j.molmet.2022.101494] [PMID: 35421611]
[74]
Wang, D.; Huang, J.; Gui, T.; Yang, Y.; Feng, T.; Tzvetkov, N.T.; Xu, T.; Gai, Z.; Zhou, Y.; Zhang, J.; Atanasov, A.G. SR-BI as a target of natural products and its significance in cancer. Semin. Cancer Biol., 2022, 80, 18-38.
[http://dx.doi.org/10.1016/j.semcancer.2019.12.025] [PMID: 31935456]
[75]
Sporstøl, M.; Tapia, G.; Malerød, L.; Mousavi, S.A.; Berg, T. Pregnane X receptor-agonists down-regulate hepatic ATP-binding cassette transporter A1 and scavenger receptor class B type I. Biochem. Biophys. Res. Commun., 2005, 331(4), 1533-1541.
[http://dx.doi.org/10.1016/j.bbrc.2005.04.071] [PMID: 15883047]
[76]
Berk, P.D. Regulatable fatty acid transport mechanisms are central to the pathophysiology of obesity, fatty liver, and metabolic syndrome. Hepatology, 2008, 48(5), 1362-1376.
[http://dx.doi.org/10.1002/hep.22632] [PMID: 18972439]
[77]
Prentice, K.J.; Saksi, J.; Hotamisligil, G.S. Adipokine FABP4 integrates energy stores and counterregulatory metabolic responses. J. Lipid Res., 2019, 60(4), 734-740.
[http://dx.doi.org/10.1194/jlr.S091793] [PMID: 30705117]
[78]
Milner, K.L.; van der Poorten, D.; Xu, A.; Bugianesi, E.; Kench, J.G.; Lam, K.S.L.; Chisholm, D.J.; George, J. Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease. Hepatology, 2009, 49(6), 1926-1934.
[http://dx.doi.org/10.1002/hep.22896] [PMID: 19475694]
[79]
Yan, L.; Yang, K.; Wang, S.; Xie, Y.; Zhang, L.; Tian, X. PXR-mediated expression of FABP4 promotes valproate-induced lipid accumulation in HepG2 cells. Toxicol. Lett., 2021, 346, 47-56.
[http://dx.doi.org/10.1016/j.toxlet.2021.04.016] [PMID: 33901630]
[80]
Zhou, J.; Febbraio, M.; Wada, T.; Zhai, Y.; Kuruba, R.; He, J.; Lee, J.H.; Khadem, S.; Ren, S.; Li, S.; Silverstein, R.L.; Xie, W. Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Gastroenterology, 2008, 134(2), 556-567.e1.
[http://dx.doi.org/10.1053/j.gastro.2007.11.037] [PMID: 18242221]
[81]
Rada, P.; González-Rodríguez, Á.; García-Monzón, C.; Valverde, Á.M. Understanding lipotoxicity in NAFLD pathogenesis: Is CD36 a key driver? Cell Death Dis., 2020, 11(9), 802.
[http://dx.doi.org/10.1038/s41419-020-03003-w] [PMID: 32978374]
[82]
Zhou, J.; Zhai, Y.; Mu, Y.; Gong, H.; Uppal, H.; Toma, D.; Ren, S.; Evans, R.M.; Xie, W. A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J. Biol. Chem., 2006, 281(21), 15013-15020.
[http://dx.doi.org/10.1074/jbc.M511116200] [PMID: 16556603]
[83]
Donnelly, K.L.; Smith, C.I.; Schwarzenberg, S.J.; Jessurun, J.; Boldt, M.D.; Parks, E.J. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J. Clin. Invest., 2005, 115(5), 1343-1351.
[http://dx.doi.org/10.1172/JCI23621] [PMID: 15864352]
[84]
Bitter, A.; Rümmele, P.; Klein, K.; Kandel, B.A.; Rieger, J.K.; Nüssler, A.K.; Zanger, U.M.; Trauner, M.; Schwab, M.; Burk, O. Pregnane X receptor activation and silencing promote steatosis of human hepatic cells by distinct lipogenic mechanisms. Arch. Toxicol., 2015, 89(11), 2089-2103.
[http://dx.doi.org/10.1007/s00204-014-1348-x] [PMID: 25182422]
[85]
Huang, J.H.; Zhang, C.; Zhang, D.G.; Li, L.; Chen, X.; Xu, D.X. Rifampicin-induced hepatic lipid accumulation: Association with up-regulation of peroxisome proliferator-activated receptor γ in mouse liver. PLoS One, 2016, 11(11), e0165787.
[http://dx.doi.org/10.1371/journal.pone.0165787] [PMID: 27806127]
[86]
Ntambi, J.; Miyazaki, M. Regulation of stearoyl-CoA desaturases and role in metabolism. Prog. Lipid Res., 2004, 43(2), 91-104.
[http://dx.doi.org/10.1016/S0163-7827(03)00039-0] [PMID: 14654089]
[87]
Zhang, J.; Wei, Y.; Hu, B.; Huang, M.; Xie, W.; Zhai, Y. Activation of human stearoyl-coenzyme A desaturase 1 contributes to the lipogenic effect of PXR in HepG2 cells. PLoS One, 2013, 8(7), e67959.
[http://dx.doi.org/10.1371/journal.pone.0067959] [PMID: 23874477]
[88]
Li, H.; Yu, X.H.; Ou, X.; Ouyang, X.P.; Tang, C.K. Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis. Prog. Lipid Res., 2021, 83, 101109.
[http://dx.doi.org/10.1016/j.plipres.2021.101109] [PMID: 34097928]
[89]
Deng, X.; Pan, X.; Cheng, C.; Liu, B.; Zhang, H.; Zhang, Y.; Xu, K. Regulation of SREBP-2 intracellular trafficking improves impaired autophagic flux and alleviates endoplasmic reticulum stress in NAFLD. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2017, 1862(3), 337-350.
[http://dx.doi.org/10.1016/j.bbalip.2016.12.007] [PMID: 28011404]
[90]
Karpale, M.; Käräjämäki, A.J.; Kummu, O.; Gylling, H.; Hyötyläinen, T.; Orešič, M.; Tolonen, A.; Hautajärvi, H.; Savolainen, M.J.; Ala-Korpela, M.; Hukkanen, J.; Hakkola, J. Activation of pregnane X receptor induces atherogenic lipids and PCSK9 by a SREBP2-mediated mechanism. Br. J. Pharmacol., 2021, 178(12), 2461-2481.
[http://dx.doi.org/10.1111/bph.15433] [PMID: 33687065]
[91]
Liu, D.; Wong, C.C.; Fu, L.; Chen, H.; Zhao, L.; Li, C.; Zhou, Y.; Zhang, Y.; Xu, W.; Yang, Y.; Wu, B.; Cheng, G.; Lai, P.B.S.; Wong, N.; Sung, J.J.Y.; Yu, J. Squalene epoxidase drives NAFLD-induced hepatocellular carcinoma and is a pharmaceutical target. Sci. Transl. Med., 2018, 10(437), eaap9840.
[http://dx.doi.org/10.1126/scitranslmed.aap9840] [PMID: 29669855]
[92]
Liu, D.; Wong, C.C.; Zhou, Y.; Li, C.; Chen, H.; Ji, F.; Go, M.Y.Y.; Wang, F.; Su, H.; Wei, H.; Cai, Z.; Wong, N.; Wong, V.W.S.; Yu, J. Squalene epoxidase induces nonalcoholic steatohepatitis via binding to carbonic anhydrase III and is a therapeutic target. Gastroenterology, 2021, 160(7), 2467-2482.e3.
[http://dx.doi.org/10.1053/j.gastro.2021.02.051] [PMID: 33647280]
[93]
Gwag, T.; Meng, Z.; Sui, Y.; Helsley, R.N.; Park, S.H.; Wang, S.; Greenberg, R.N.; Zhou, C. Non-nucleoside reverse transcriptase inhibitor efavirenz activates PXR to induce hypercholesterolemia and hepatic steatosis. J. Hepatol., 2019, 70(5), 930-940.
[http://dx.doi.org/10.1016/j.jhep.2018.12.038] [PMID: 30677459]
[94]
Loomba, R.; Friedman, S.L.; Shulman, G.I. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell, 2021, 184(10), 2537-2564.
[http://dx.doi.org/10.1016/j.cell.2021.04.015] [PMID: 33989548]
[95]
Nakamura, K.; Moore, R.; Negishi, M.; Sueyoshi, T. Nuclear pregnane X receptor cross-talk with FoxA2 to mediate drug-induced regulation of lipid metabolism in fasting mouse liver. J. Biol. Chem., 2007, 282(13), 9768-9776.
[http://dx.doi.org/10.1074/jbc.M610072200] [PMID: 17267396]
[96]
Tahri-Joutey, M.; Andreoletti, P.; Surapureddi, S.; Nasser, B.; Cherkaoui-Malki, M.; Latruffe, N. Mechanisms Mediating the Regulation of Peroxisomal Fatty Acid Beta-Oxidation by PPARα. Int. J. Mol. Sci., 2021, 22(16), 8969.
[http://dx.doi.org/10.3390/ijms22168969] [PMID: 34445672]
[97]
Chen, L.; Chen, X.W.; Huang, X.; Song, B.L.; Wang, Y.; Wang, Y. Regulation of glucose and lipid metabolism in health and disease. Sci. China Life Sci., 2019, 62(11), 1420-1458.
[http://dx.doi.org/10.1007/s11427-019-1563-3] [PMID: 31686320]
[98]
Hassani-Nezhad-Gashti, F.; Rysä, J.; Kummu, O.; Näpänkangas, J.; Buler, M.; Karpale, M.; Hukkanen, J.; Hakkola, J. Activation of nuclear receptor PXR impairs glucose tolerance and dysregulates GLUT2 expression and subcellular localization in liver. Biochem. Pharmacol., 2018, 148, 253-264.
[http://dx.doi.org/10.1016/j.bcp.2018.01.001] [PMID: 29309761]
[99]
Cui, J.Y.; Gunewardena, S.S.; Rockwell, C.E.; Klaassen, C.D. ChIPing the cistrome of PXR in mouse liver. Nucleic Acids Res., 2010, 38(22), 7943-7963.
[http://dx.doi.org/10.1093/nar/gkq654] [PMID: 20693526]
[100]
Liu, P.; Jiang, L.; Kong, W.; Xie, Q.; Li, P.; Liu, X.; Zhang, J.; Liu, M.; Wang, Z.; Zhu, L.; Yang, H.; Zhou, Y.; Zou, J.; Liu, X.; Liu, L. PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α–GLUT2 pathway. Acta Pharm. Sin. B, 2022, 12(5), 2391-2405.
[http://dx.doi.org/10.1016/j.apsb.2021.09.031] [PMID: 35646519]
[101]
Spruiell, K.; Richardson, R.M.; Cullen, J.M.; Awumey, E.M.; Gonzalez, F.J.; Gyamfi, M.A. Role of pregnane X receptor in obesity and glucose homeostasis in male mice. J. Biol. Chem., 2014, 289(6), 3244-3261.
[http://dx.doi.org/10.1074/jbc.M113.494575] [PMID: 24362030]
[102]
Ling, Z.; Shu, N.; Xu, P.; Wang, F.; Zhong, Z.; Sun, B.; Li, F.; Zhang, M.; Zhao, K.; Tang, X.; Wang, Z.; Zhu, L.; Liu, L.; Liu, X. Involvement of pregnane X receptor in the impaired glucose utilization induced by atorvastatin in hepatocytes. Biochem. Pharmacol., 2016, 100, 98-111.
[http://dx.doi.org/10.1016/j.bcp.2015.11.023] [PMID: 26616219]
[103]
Rui, L. Energy metabolism in the liver. Compr. Physiol., 2014, 4(1), 177-197.
[http://dx.doi.org/10.1002/cphy.c130024] [PMID: 24692138]
[104]
Kodama, S.; Moore, R.; Yamamoto, Y.; Negishi, M. Human nuclear pregnane X receptor cross-talk with CREB to repress cAMP activation of the glucose-6-phosphatase gene. Biochem. J., 2007, 407(3), 373-381.
[http://dx.doi.org/10.1042/BJ20070481] [PMID: 17635106]
[105]
Wang, P.; Shao, X.; Bao, Y.; Zhu, J.; Chen, L.; Zhang, L.; Ma, X.; Zhong, X. Impact of obese levels on the hepatic expression of nuclear receptors and drug-metabolizing enzymes in adult and offspring mice. Acta Pharm. Sin. B, 2020, 10(1), 171-185.
[http://dx.doi.org/10.1016/j.apsb.2019.10.009] [PMID: 31993314]
[106]
Jamwal, R.; de la Monte, S.M.; Ogasawara, K.; Adusumalli, S.; Barlock, B.B.; Akhlaghi, F. Nonalcoholic fatty liver disease and diabetes are associated with decreased CYP3A4 protein expression and activity in human liver. Mol. Pharm., 2018, 15(7), 2621-2632.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00159] [PMID: 29792708]
[107]
Fisher, C.D.; Lickteig, A.J.; Augustine, L.M.; Ranger-Moore, J.; Jackson, J.P.; Ferguson, S.S.; Cherrington, N.J. Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metab. Dispos., 2009, 37(10), 2087-2094.
[http://dx.doi.org/10.1124/dmd.109.027466] [PMID: 19651758]
[108]
Bell, L.N.; Temm, C.J.; Saxena, R.; Vuppalanchi, R.; Schauer, P.; Rabinovitz, M.; Krasinskas, A.; Chalasani, N.; Mattar, S.G. Bariatric surgery-induced weight loss reduces hepatic lipid peroxidation levels and affects hepatic cytochrome P-450 protein content. Ann. Surg., 2010, 251(6), 1041-1048.
[http://dx.doi.org/10.1097/SLA.0b013e3181dbb572] [PMID: 20485142]
[109]
Li, X.; Wang, Z.; Klaunig, J.E. Modulation of xenobiotic nuclear receptors in high-fat diet induced non-alcoholic fatty liver disease. Toxicology, 2018, 410, 199-213.
[http://dx.doi.org/10.1016/j.tox.2018.08.007] [PMID: 30120929]
[110]
Sepe, V.; D’Amore, C.; Ummarino, R.; Renga, B.; D’Auria, M.V.; Novellino, E.; Sinisi, A.; Taglialatela-Scafati, O.; Nakao, Y.; Limongelli, V.; Zampella, A.; Fiorucci, S. Insights on pregnane-X-receptor modulation. Natural and semisynthetic steroids from Theonella marine sponges. Eur. J. Med. Chem., 2014, 73, 126-134.
[http://dx.doi.org/10.1016/j.ejmech.2013.12.005] [PMID: 24388834]
[111]
Yoneda, M.; Endo, H.; Mawatari, H.; Nozaki, Y.; Fujita, K.; Akiyama, T.; Higurashi, T.; Uchiyama, T.; Yoneda, K.; Takahashi, H.; Kirikoshi, H.; Inamori, M.; Abe, Y.; Kubota, K.; Saito, S.; Kobayashi, N.; Yamaguchi, N.; Maeyama, S.; Yamamoto, S.; Tsutsumi, S.; Aburatani, H.; Wada, K.; Hotta, K.; Nakajima, A. Gene expression profiling of non-alcoholic steatohepatitis using gene set enrichment analysis. Hepatol. Res., 2008, 38(1204), 12.
[http://dx.doi.org/10.1111/j.1872-034X.2008.00399.x] [PMID: 18637145]
[112]
Ma, X.; Zheng, X.; Liu, S.; Zhuang, L.; Wang, M.; Wang, Y.; Xin, Y.; Xuan, S. Relationship of circulating total bilirubin, UDP-glucuronosyltransferases 1A1 and the development of non-alcoholic fatty liver disease: A cross-sectional study. BMC Gastroenterol., 2022, 22(1), 6.
[http://dx.doi.org/10.1186/s12876-021-02088-7] [PMID: 34986792]
[113]
Zhu, H.; Chen, Z.; Ma, Z.; Tan, H.; Xiao, C.; Tang, X.; Zhang, B.; Wang, Y.; Gao, Y. Tanshinone IIA protects endothelial cells from H 2 O 2 -induced injuries via PXR activation. Biomol. Ther., 2017, 25(6), 599-608.
[http://dx.doi.org/10.4062/biomolther.2016.179] [PMID: 28173640]
[114]
Harmsen, S.; Meijerman, I.; Beijnen, J.H.; Schellens, J.H.M. The role of nuclear receptors in pharmacokinetic drug–drug interactions in oncology. Cancer Treat. Rev., 2007, 33(4), 369-380.
[http://dx.doi.org/10.1016/j.ctrv.2007.02.003] [PMID: 17451886]
[115]
Kolwankar, D.; Vuppalanchi, R.; Ethell, B.; Jones, D.R.; Wrighton, S.A.; Hall, S.D.; Chalasani, N. Association between nonalcoholic hepatic steatosis and hepatic cytochrome P-450 3A activity. Clin. Gastroenterol. Hepatol., 2007, 5(3), 388-393.
[http://dx.doi.org/10.1016/j.cgh.2006.12.021] [PMID: 17368239]
[116]
Woolsey, S.J.; Beaton, M.D.; Mansell, S.E.; Leon-Ponte, M.; Yu, J.; Pin, C.L.; Adams, P.C.; Kim, R.B.; Tirona, R.G. A fibroblast growth factor 21–pregnane X receptor pathway downregulates hepatic CYP3A4 in nonalcoholic fatty liver disease. Mol. Pharmacol., 2016, 90(4), 437-446.
[http://dx.doi.org/10.1124/mol.116.104687] [PMID: 27482056]
[117]
Yan, J.; Xie, W. A brief history of the discovery of PXR and CAR as xenobiotic receptors. Acta Pharm. Sin. B, 2016, 6(5), 450-452.
[http://dx.doi.org/10.1016/j.apsb.2016.06.011] [PMID: 27709013]
[118]
Nigam, S.K. What do drug transporters really do? Nat. Rev. Drug Discov., 2015, 14(1), 29-44.
[http://dx.doi.org/10.1038/nrd4461] [PMID: 25475361]
[119]
Rosenthal, S.B.; Bush, K.T.; Nigam, S.K. A network of SLC and ABC transporter and DME genes involved in remote sensing and signaling in the gut-liver-kidney axis. Sci. Rep., 2019, 9(1), 11879.
[http://dx.doi.org/10.1038/s41598-019-47798-x] [PMID: 31417100]
[120]
Zeng, H.; Lin, Y.; Gong, J.; Lin, S.; Gao, J.; Li, C.; Feng, Z.; Zhang, H.; Zhang, J.; Li, Y.; Yu, C. CYP3A suppression during diet-induced nonalcoholic fatty liver disease is independent of PXR regulation. Chem. Biol. Interact., 2019, 308, 185-193.
[http://dx.doi.org/10.1016/j.cbi.2019.05.038] [PMID: 31132328]
[121]
Sui, Y.; Meng, Z.; Park, S.H.; Lu, W.; Livelo, C.; Chen, Q.; Zhou, T.; Zhou, C. Myeloid-specific deficiency of pregnane X receptor decreases atherosclerosis in LDL receptor-deficient mice. J. Lipid Res., 2020, 61(5), 696-706.
[http://dx.doi.org/10.1194/jlr.RA119000122] [PMID: 32170024]
[122]
Mridha, A.R.; Wree, A.; Robertson, A.A.B.; Yeh, M.M.; Johnson, C.D.; Van Rooyen, D.M.; Haczeyni, F.; Teoh, N.C.H.; Savard, C.; Ioannou, G.N.; Masters, S.L.; Schroder, K.; Cooper, M.A.; Feldstein, A.E.; Farrell, G.C. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. J. Hepatol., 2017, 66(5), 1037-1046.
[http://dx.doi.org/10.1016/j.jhep.2017.01.022] [PMID: 28167322]
[123]
Alegre, F.; Pelegrin, P.; Feldstein, A. Inflammasomes in liver fibrosis. Semin. Liver Dis., 2017, 37(2), 119-127.
[http://dx.doi.org/10.1055/s-0037-1601350] [PMID: 28564720]
[124]
Wang, S.; Lei, T.; Zhang, K.; Zhao, W.; Fang, L.; Lai, B.; Han, J.; Xiao, L.; Wang, N. Xenobiotic pregnane X receptor (PXR) regulates innate immunity via activation of NLRP3 inflammasome in vascular endothelial cells. J. Biol. Chem., 2014, 289(43), 30075-30081.
[http://dx.doi.org/10.1074/jbc.M114.578781] [PMID: 25202020]
[125]
Hudson, G.; Flannigan, K.L.; Venu, V.K.P.; Alston, L.; Sandall, C.F.; MacDonald, J.A.; Muruve, D.A.; Chang, T.K.H.; Mani, S.; Hirota, S.A. Pregnane X receptor activation triggers rapid atp release in primed macrophages that mediates nlrp3 inflammasome activation. J. Pharmacol. Exp. Ther., 2019, 370(1), 44-53.
[http://dx.doi.org/10.1124/jpet.118.255679] [PMID: 31004077]
[126]
Krenkel, O.; Tacke, F. Liver macrophages in tissue homeostasis and disease. Nat. Rev. Immunol., 2017, 17(5), 306-321.
[http://dx.doi.org/10.1038/nri.2017.11] [PMID: 28317925]
[127]
Deuring, J.J.; Li, M.; Cao, W.; Chen, S.; Wang, W.; de Haar, C.; van der Woude, C.J.; Peppelenbosch, M. Pregnane X receptor activation constrains mucosal NF-κB activity in active inflammatory bowel disease. PLoS One, 2019, 14(10), e0221924.
[http://dx.doi.org/10.1371/journal.pone.0221924] [PMID: 31581194]
[128]
Sun, M.; Cui, W.; Woody, S.K.; Staudinger, J.L. Pregnane X receptor modulates the inflammatory response in primary cultures of hepatocytes. Drug Metab. Dispos., 2015, 43(3), 335-343.
[http://dx.doi.org/10.1124/dmd.114.062307] [PMID: 25527709]
[129]
Okamura, M.; Shizu, R.; Abe, T.; Kodama, S.; Hosaka, T.; Sasaki, T.; Yoshinari, K. PXR functionally interacts with NF-κB and AP-1 to Downregulate the inflammation-induced expression of chemokine CXCL2 in mice. Cells, 2020, 9(10), 2296.
[http://dx.doi.org/10.3390/cells9102296] [PMID: 33076328]
[130]
Erickson, S.L.; Alston, L.; Nieves, K.; Chang, T.K.H.; Mani, S.; Flannigan, K.L.; Hirota, S.A. The xenobiotic sensing pregnane X receptor regulates tissue damage and inflammation triggered by C difficile toxins. FASEB J., 2020, 34(2), 2198-2212.
[http://dx.doi.org/10.1096/fj.201902083RR] [PMID: 31907988]
[131]
Amer, A.O.; Probert, P.M.; Dunn, M.; Knight, M.; Vallance, A.E.; Flecknell, P.A.; Oakley, F.; Cameron, I.; White, S.A.; Blain, P.G.; Wright, M.C. Sustained isoprostane E2 elevation, inflammation and fibrosis after acute ischaemia-reperfusion injury are reduced by pregnane X receptor activation. PLoS One, 2015, 10(8), e0136173.
[http://dx.doi.org/10.1371/journal.pone.0136173] [PMID: 26302150]
[132]
Zhou, C.; Tabb, M.M.; Nelson, E.L.; Grün, F.; Verma, S.; Sadatrafiei, A.; Lin, M.; Mallick, S.; Forman, B.M.; Thummel, K.E.; Blumberg, B. Mutual repression between steroid and xenobiotic receptor and NF- B signaling pathways links xenobiotic metabolism and inflammation. J. Clin. Invest., 2006, 116(8), 2280-2289.
[http://dx.doi.org/10.1172/JCI26283] [PMID: 16841097]
[133]
Venkatesh, M.; Mukherjee, S.; Wang, H.; Li, H.; Sun, K.; Benechet, A.P.; Qiu, Z.; Maher, L.; Redinbo, M.R.; Phillips, R.S.; Fleet, J.C.; Kortagere, S.; Mukherjee, P.; Fasano, A.; Le Ven, J.; Nicholson, J.K.; Dumas, M.E.; Khanna, K.M.; Mani, S. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity, 2014, 41(2), 296-310.
[http://dx.doi.org/10.1016/j.immuni.2014.06.014] [PMID: 25065623]
[134]
Stienstra, R.; van Diepen, J.A.; Tack, C.J.; Zaki, M.H.; van de Veerdonk, F.L.; Perera, D.; Neale, G.A.; Hooiveld, G.J.; Hijmans, A.; Vroegrijk, I.; van den Berg, S.; Romijn, J.; Rensen, P.C.N.; Joosten, L.A.B.; Netea, M.G.; Kanneganti, T.D. Inflammasome is a central player in the induction of obesity and insulin resistance. Proc. Natl. Acad. Sci. USA, 2011, 108(37), 15324-15329.
[http://dx.doi.org/10.1073/pnas.1100255108] [PMID: 21876127]
[135]
Henao-Mejia, J.; Elinav, E.; Jin, C.; Hao, L.; Mehal, W.Z.; Strowig, T.; Thaiss, C.A.; Kau, A.L.; Eisenbarth, S.C.; Jurczak, M.J.; Camporez, J.P.; Shulman, G.I.; Gordon, J.I.; Hoffman, H.M.; Flavell, R.A. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature, 2012, 482(7384), 179-185.
[http://dx.doi.org/10.1038/nature10809] [PMID: 22297845]
[136]
Sunny, N.E.; Parks, E.J.; Browning, J.D.; Burgess, S.C. Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease. Cell Metab., 2011, 14(6), 804-810.
[http://dx.doi.org/10.1016/j.cmet.2011.11.004] [PMID: 22152305]
[137]
Koliaki, C.; Szendroedi, J.; Kaul, K.; Jelenik, T.; Nowotny, P.; Jankowiak, F.; Herder, C.; Carstensen, M.; Krausch, M.; Knoefel, W.T.; Schlensak, M.; Roden, M. Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. Cell Metab., 2015, 21(5), 739-746.
[http://dx.doi.org/10.1016/j.cmet.2015.04.004] [PMID: 25955209]
[138]
Satapati, S.; Kucejova, B.; Duarte, J.A.G.; Fletcher, J.A.; Reynolds, L.; Sunny, N.E.; He, T.; Nair, L.A.; Livingston, K.; Fu, X.; Merritt, M.E.; Sherry, A.D.; Malloy, C.R.; Shelton, J.M.; Lambert, J.; Parks, E.J.; Corbin, I.; Magnuson, M.A.; Browning, J.D.; Burgess, S.C. Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. J. Clin. Invest., 2015, 125(12), 4447-4462.
[http://dx.doi.org/10.1172/JCI82204] [PMID: 26571396]
[139]
Nagahori, H.; Nakamura, K.; Sumida, K.; Ito, S.; Ohtsuki, S. Combining genomics to identify the pathways of post-transcriptional nongenotoxic signaling and energy homeostasis in livers of rats treated with the pregnane x receptor agonist, pregnenolone carbonitrile. J. Proteome Res., 2017, 16(10), 3634-3645.
[http://dx.doi.org/10.1021/acs.jproteome.7b00364] [PMID: 28825834]
[140]
Urquhart, B.L.; Tirona, R.G.; Kim, R.B. Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: Implications for interindividual variability in response to drugs. J. Clin. Pharmacol., 2007, 47(5), 566-578.
[http://dx.doi.org/10.1177/0091270007299930] [PMID: 17442683]
[141]
Gong, H.; Singh, S.V.; Singh, S.P.; Mu, Y.; Lee, J.H.; Saini, S.P.S.; Toma, D.; Ren, S.; Kagan, V.E.; Day, B.W.; Zimniak, P.; Xie, W. Orphan nuclear receptor pregnane X receptor sensitizes oxidative stress responses in transgenic mice and cancerous cells. Mol. Endocrinol., 2006, 20(2), 279-290.
[http://dx.doi.org/10.1210/me.2005-0205] [PMID: 16195250]
[142]
Xie, Y.; Xu, M.; Deng, M.; Li, Z.; Wang, P.; Ren, S.; Guo, Y.; Ma, X.; Fan, J.; Billiar, T.R.; Xie, W. Activation of pregnane X receptor sensitizes mice to hemorrhagic shock–induced liver injury. Hepatology, 2019, 70(3), 995-1010.
[http://dx.doi.org/10.1002/hep.30691] [PMID: 31038762]
[143]
Swales, K.E.; Moore, R.; Truss, N.J.; Tucker, A.; Warner, T.D.; Negishi, M.; Bishop-Bailey, D. Pregnane X receptor regulates drug metabolism and transport in the vasculature and protects from oxidative stress. Cardiovasc. Res., 2012, 93(4), 674-681.
[http://dx.doi.org/10.1093/cvr/cvr330] [PMID: 22166712]
[144]
Czaja, M.J. Function of autophagy in nonalcoholic fatty liver disease. Dig. Dis. Sci., 2016, 61(5), 1304-1313.
[http://dx.doi.org/10.1007/s10620-015-4025-x] [PMID: 26725058]
[145]
Lee, Y.A.; Noon, L.A.; Akat, K.M.; Ybanez, M.D.; Lee, T.F.; Berres, M.L.; Fujiwara, N.; Goossens, N.; Chou, H.I.; Parvin-Nejad, F.P.; Khambu, B.; Kramer, E.G.M.; Gordon, R.; Pfleger, C.; Germain, D.; John, G.R.; Campbell, K.N.; Yue, Z.; Yin, X.M.; Cuervo, A.M.; Czaja, M.J.; Fiel, M.I.; Hoshida, Y.; Friedman, S.L. Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap. Nat. Commun., 2018, 9(1), 4962.
[http://dx.doi.org/10.1038/s41467-018-07338-z] [PMID: 30470740]
[146]
Singh, R.; Kaushik, S.; Wang, Y.; Xiang, Y.; Novak, I.; Komatsu, M.; Tanaka, K.; Cuervo, A.M.; Czaja, M.J. Autophagy regulates lipid metabolism. Nature, 2009, 458(7242), 1131-1135.
[http://dx.doi.org/10.1038/nature07976] [PMID: 19339967]
[147]
Chen, C.L.; Lin, Y.C. Autophagy dysregulation in metabolic associated fatty liver disease: A new therapeutic target. Int. J. Mol. Sci., 2022, 23(17), 10055.
[http://dx.doi.org/10.3390/ijms231710055] [PMID: 36077452]
[148]
Yan, L.; Chen, Z.; Wu, L.; Su, Y.; Wang, X.; Tang, N. Inhibitory effect of PXR on ammonia-induced hepatocyte autophagy via P53. Toxicol. Lett., 2018, 295, 153-161.
[http://dx.doi.org/10.1016/j.toxlet.2018.06.1066] [PMID: 29908302]
[149]
Kodama, S.; Negishi, M. PXR cross-talks with internal and external signals in physiological and pathophysiological responses. Drug Metab. Rev., 2013, 45(3), 300-310.
[http://dx.doi.org/10.3109/03602532.2013.795585] [PMID: 23701014]
[150]
Li, H.; Gong, W.; Wang, G.; Yu, E.; Tian, J.; Xia, Y.; Li, Z.; Zhang, K.; Xie, J. Role of nuclear pregnane X receptor in Cu-induced lipid metabolism and xenobiotic responses in largemouth bass (Micropterus salmoides). Front. Endocrinol., 2022, 13, 950985.
[http://dx.doi.org/10.3389/fendo.2022.950985] [PMID: 35966089]
[151]
Nakagawa, H.; Umemura, A.; Taniguchi, K.; Font-Burgada, J.; Dhar, D.; Ogata, H.; Zhong, Z.; Valasek, M.A.; Seki, E.; Hidalgo, J.; Koike, K.; Kaufman, R.J.; Karin, M. ER stress cooperates with hypernutrition to trigger TNF-dependent spontaneous HCC development. Cancer Cell, 2014, 26(3), 331-343.
[http://dx.doi.org/10.1016/j.ccr.2014.07.001] [PMID: 25132496]
[152]
Maurel, M.; Samali, A.; Chevet, E. Endoplasmic reticulum stress: At the crossroads of inflammation and metabolism in hepatocellular carcinoma development. Cancer Cell, 2014, 26(3), 301-303.
[http://dx.doi.org/10.1016/j.ccr.2014.08.007] [PMID: 25203316]
[153]
Shehu, A.I.; Lu, J.; Wang, P.; Zhu, J.; Wang, Y.; Yang, D.; McMahon, D.; Xie, W.; Gonzalez, F.J.; Ma, X. Pregnane X receptor activation potentiates ritonavir hepatotoxicity. J. Clin. Invest., 2019, 129(7), 2898-2903.
[http://dx.doi.org/10.1172/JCI128274] [PMID: 31039134]
[154]
Vachirayonsti, T.; Ho, K.W.; Yang, D.; Yan, B. Suppression of the pregnane X receptor during endoplasmic reticulum stress is achieved by down-regulating hepatocyte nuclear factor-4α and up-regulating liver-enriched inhibitory protein. Toxicol. Sci., 2015, 144(2), 382-392.
[http://dx.doi.org/10.1093/toxsci/kfv008] [PMID: 25616597]
[155]
Dulai, P.S.; Singh, S.; Patel, J.; Soni, M.; Prokop, L.J.; Younossi, Z.; Sebastiani, G.; Ekstedt, M.; Hagstrom, H.; Nasr, P.; Stal, P.; Wong, V.W.S.; Kechagias, S.; Hultcrantz, R.; Loomba, R. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: Systematic review and meta‐analysis. Hepatology, 2017, 65(5), 1557-1565.
[http://dx.doi.org/10.1002/hep.29085] [PMID: 28130788]
[156]
Sanyal, A.J.; Harrison, S.A.; Ratziu, V.; Abdelmalek, M.F.; Diehl, A.M.; Caldwell, S.; Shiffman, M.L.; Aguilar Schall, R.; Jia, C.; McColgan, B.; Djedjos, C.S.; McHutchison, J.G.; Subramanian, G.M.; Myers, R.P.; Younossi, Z.; Muir, A.J.; Afdhal, N.H.; Bosch, J.; Goodman, Z. The natural history of advanced fibrosis due to nonalcoholic steatohepatitis: Data from the simtuzumab trials. Hepatology, 2019, 70(6), 1913-1927.
[http://dx.doi.org/10.1002/hep.30664] [PMID: 30993748]
[157]
Tsuchida, T.; Friedman, S.L. Mechanisms of hepatic stellate cell activation. Nat. Rev. Gastroenterol. Hepatol., 2017, 14(7), 397-411.
[http://dx.doi.org/10.1038/nrgastro.2017.38] [PMID: 28487545]
[158]
Lade, A.; Noon, L.A.; Friedman, S.L. Contributions of metabolic dysregulation and inflammation to nonalcoholic steatohepatitis, hepatic fibrosis, and cancer. Curr. Opin. Oncol., 2014, 26(1), 100-107.
[http://dx.doi.org/10.1097/CCO.0000000000000042] [PMID: 24275855]
[159]
Mohandas, S.; Vairappan, B. Role of pregnane X-receptor in regulating bacterial translocation in chronic liver diseases. World J. Hepatol., 2017, 9(32), 1210-1226.
[http://dx.doi.org/10.4254/wjh.v9.i32.1210] [PMID: 29184608]
[160]
Wright, M.C. The impact of pregnane X receptor activation on liver fibrosis. Biochem. Soc. Trans., 2006, 34(6), 1119-1123.
[http://dx.doi.org/10.1042/BST0341119] [PMID: 17073765]
[161]
Li, X.; Wang, Z.; Klaunig, J.J.T. The effects of perfluorooctanoate on high fat diet induced non-alcoholic fatty liver disease in mice. Toxicology, 2019, 416, 1-14.
[http://dx.doi.org/10.1016/j.tox.2019.01.017]
[162]
Yetti, H.; Naito, H.; Yuan, Y.; Jia, X.; Hayashi, Y. Bile acid detoxifying enzymes limit susceptibility to liver fibrosis in female SHRSP5/Dmcr rats fed with a high-fat-cholesterol diet. PLoS One., 2018, 13(2), e0192863.
[163]
Wallace, K.; Cowie, D.E.; Konstantinou, D.K.; Hill, S.J.; Tjelle, T.E.; Axon, A.; Koruth, M.; White, S.A.; Carlsen, H.; Mann, D.A.; Wright, M.C. The PXR is a drug target for chronic inflammatory liver disease. J. Steroid Biochem. Mol. Biol., 2010, 120(2-3), 137-148.
[http://dx.doi.org/10.1016/j.jsbmb.2010.04.012] [PMID: 20416375]
[164]
Caussy, C.; Tripathi, A.; Humphrey, G.; Bassirian, S.; Singh, S.; Faulkner, C.; Bettencourt, R.; Rizo, E.; Richards, L.; Xu, Z.Z.; Downes, M.R.; Evans, R.M.; Brenner, D.A.; Sirlin, C.B.; Knight, R.; Loomba, R. A gut microbiome signature for cirrhosis due to nonalcoholic fatty liver disease. Nat. Commun., 2019, 10(1), 1406.
[http://dx.doi.org/10.1038/s41467-019-09455-9] [PMID: 30926798]
[165]
Da Silva, H.E.; Teterina, A.; Comelli, E.M.; Taibi, A.; Arendt, B.M.; Fischer, S.E.; Lou, W.; Allard, J.P. Nonalcoholic fatty liver disease is associated with dysbiosis independent of body mass index and insulin resistance. Sci. Rep., 2018, 8(1), 1466.
[http://dx.doi.org/10.1038/s41598-018-19753-9] [PMID: 29362454]
[166]
Loomba, R.; Seguritan, V.; Li, W.; Long, T.; Klitgord, N.; Bhatt, A.; Dulai, P.S.; Caussy, C.; Bettencourt, R.; Highlander, S.K.; Jones, M.B.; Sirlin, C.B.; Schnabl, B.; Brinkac, L.; Schork, N.; Chen, C.H.; Brenner, D.A.; Biggs, W.; Yooseph, S.; Venter, J.C.; Nelson, K.E. Gut microbiome-based metagenomic signature for non-invasive detection of advanced fibrosis in human nonalcoholic fatty liver disease. Cell Metab., 2017, 25(5), 1054-1062.e5.
[http://dx.doi.org/10.1016/j.cmet.2017.04.001] [PMID: 28467925]
[167]
Oh, T.G.; Kim, S.M.; Caussy, C.; Fu, T.; Guo, J.; Bassirian, S.; Singh, S.; Madamba, E.V.; Bettencourt, R.; Richards, L.; Yu, R.T.; Atkins, A.R.; Huan, T.; Brenner, D.A.; Sirlin, C.B.; Downes, M.; Evans, R.M.; Loomba, R. A universal gut-microbiome-derived signature predicts cirrhosis. Cell Metab., 2020, 32(5), 878-888.e6.
[http://dx.doi.org/10.1016/j.cmet.2020.06.005] [PMID: 32610095]
[168]
Schwimmer, J.B.; Johnson, J.S.; Angeles, J.E.; Behling, C.; Belt, P.H.; Borecki, I.; Bross, C.; Durelle, J.; Goyal, N.P.; Hamilton, G.; Holtz, M.L.; Lavine, J.E.; Mitreva, M.; Newton, K.P.; Pan, A.; Simpson, P.M.; Sirlin, C.B.; Sodergren, E.; Tyagi, R.; Yates, K.P.; Weinstock, G.M.; Salzman, N.H. Microbiome signatures associated with steatohepatitis and moderate to severe fibrosis in children with nonalcoholic fatty liver disease. Gastroenterology, 2019, 157(4), 1109-1122.
[http://dx.doi.org/10.1053/j.gastro.2019.06.028] [PMID: 31255652]
[169]
Sharpton, S.R.; Ajmera, V.; Loomba, R. Emerging role of the gut microbiome in nonalcoholic fatty liver disease: From composition to function. Clin. Gastroenterol. Hepatol., 2019, 17(2), 296-306.
[http://dx.doi.org/10.1016/j.cgh.2018.08.065] [PMID: 30196156]
[170]
Barretto, S.A.; Lasserre, F.; Huillet, M.; Régnier, M.; Polizzi, A.; Lippi, Y.; Fougerat, A.; Person, E.; Bruel, S.; Bétoulières, C.; Naylies, C.; Lukowicz, C.; Smati, S.; Guzylack, L.; Olier, M.; Théodorou, V.; Mselli-Lakhal, L.; Zalko, D.; Wahli, W.; Loiseau, N.; Gamet-Payrastre, L.; Guillou, H.; Ellero-Simatos, S. The pregnane X receptor drives sexually dimorphic hepatic changes in lipid and xenobiotic metabolism in response to gut microbiota in mice. Microbiome, 2021, 9(1), 93.
[http://dx.doi.org/10.1186/s40168-021-01050-9] [PMID: 33879258]
[171]
Dempsey, J.L.; Cui, J.Y. Microbiome is a functional modifier of P450 drug metabolism. Curr. Pharmacol. Rep., 2019, 5(6), 481-490.
[http://dx.doi.org/10.1007/s40495-019-00200-w] [PMID: 33312848]
[172]
Zhao, X.; Zhou, J.; Liang, W.; Sheng, Q.; Lu, L.; Chen, T.; Chen, J.; Tan, K.; Lv, Z. Probiotics mixture reinforces barrier function to ameliorate necrotizing enterocolitis by regulating PXR-JNK pathway. Cell Biosci., 2021, 11(1), 20.
[http://dx.doi.org/10.1186/s13578-021-00530-7] [PMID: 33482929]
[173]
Dempsey, J.L.; Wang, D.; Siginir, G.; Fei, Q.; Raftery, D.; Gu, H.; Yue Cui, J. Pharmacological activation of PXR and CAR downregulates distinct bile acid-metabolizing intestinal bacteria and alters bile acid homeostasis. Toxicol. Sci., 2019, 168(1), 40-60.
[http://dx.doi.org/10.1093/toxsci/kfy271] [PMID: 30407581]
[174]
Simrén, M.; Tack, J. New treatments and therapeutic targets for IBS and other functional bowel disorders. Nat. Rev. Gastroenterol. Hepatol., 2018, 15(10), 589-605.
[http://dx.doi.org/10.1038/s41575-018-0034-5] [PMID: 29930260]
[175]
Ning, L.; Lou, X.; Zhang, F.; Xu, G. Nuclear receptors in the pathogenesis and management of inflammatory bowel disease. Mediators Inflamm., 2019, 2019, 1-13.
[http://dx.doi.org/10.1155/2019/2624941] [PMID: 30804707]
[176]
Lopetuso, L.R.; Napoli, M.; Rizzatti, G.; Gasbarrini, A. The intriguing role of Rifaximin in gut barrier chronic inflammation and in the treatment of Crohn’s disease. Expert Opin. Investig. Drugs, 2018, 27(6), 543-551.
[http://dx.doi.org/10.1080/13543784.2018.1483333] [PMID: 29865875]
[177]
Webb, G.J.; Rahman, S.R.; Levy, C.; Hirschfield, G.M. Low risk of hepatotoxicity from rifampicin when used for cholestatic pruritus: A cross-disease cohort study. Aliment. Pharmacol. Ther., 2018, 47(8), 1213-1219.
[http://dx.doi.org/10.1111/apt.14579] [PMID: 29468705]
[178]
Tuohutaerbieke, M.; Li, X.; Yin, Y.; Chen, W.; Wu, D.; Mao, Z.; Mamuerjiang, J.; Mao, Y.; Shen, T. The characteristics, prevalence, and risk factors of drug-induced liver injury among brucellosis inpatients in Xinjiang, China. Front. Pharmacol., 2021, 12, 657805.
[http://dx.doi.org/10.3389/fphar.2021.657805] [PMID: 34040524]
[179]
Wang, J.Y.; Tsai, C.H.; Lee, Y.L.; Lee, L.N.; Hsu, C.L.; Chang, H.C.; Chen, J.M.; Hsu, C.A.; Yu, C.J.; Yang, P.C. Gender-dimorphic impact of pxr genotype and haplotype on hepatotoxicity during antituberculosis treatment. Medicine, 2015, 94(24), e982.
[http://dx.doi.org/10.1097/MD.0000000000000982] [PMID: 26091473]
[180]
zhang, X.; Ma, Z.; Liang, Q.; Tang, X.; Hu, D.; Liu, C.; Tan, H.; Xiao, C.; Zhang, B.; Wang, Y.; Gao, Y. Tanshinone IIA exerts protective effects in a LCA-induced cholestatic liver model associated with participation of pregnane X receptor. J. Ethnopharmacol., 2015, 164, 357-367.
[http://dx.doi.org/10.1016/j.jep.2015.01.047] [PMID: 25660334]
[181]
Ekins, S.; Kholodovych, V.; Ai, N.; Sinz, M.; Gal, J.; Gera, L.; Welsh, W.J.; Bachmann, K.; Mani, S. Computational discovery of novel low micromolar human pregnane X receptor antagonists. Mol. Pharmacol., 2008, 74(3), 662-672.
[http://dx.doi.org/10.1124/mol.108.049437] [PMID: 18579710]
[182]
Li, F.; Lu, J.; Cheng, J.; Wang, L.; Matsubara, T.; Csanaky, I.L.; Klaassen, C.D.; Gonzalez, F.J.; Ma, X. Human PXR modulates hepatotoxicity associated with rifampicin and isoniazid co-therapy. Nat. Med., 2013, 19(4), 418-420.
[http://dx.doi.org/10.1038/nm.3104] [PMID: 23475203]
[183]
Healan-Greenberg, C.; Waring, J.F.; Kempf, D.J.; Blomme, E.A.G.; Tirona, R.G.; Kim, R.B. A human immunodeficiency virus protease inhibitor is a novel functional inhibitor of human pregnane X receptor. Drug Metab. Dispos., 2008, 36(3), 500-507.
[http://dx.doi.org/10.1124/dmd.107.019547] [PMID: 18096673]
[184]
Ma, X.; Shah, Y.M.; Guo, G.L.; Wang, T.; Krausz, K.W.; Idle, J.R.; Gonzalez, F.J. Rifaximin is a gut-specific human pregnane X receptor activator. J. Pharmacol. Exp. Ther., 2007, 322(1), 391-398.
[http://dx.doi.org/10.1124/jpet.107.121913] [PMID: 17442842]
[185]
Mani, S.; Dou, W.; Redinbo, M.R. PXR antagonists and implication in drug metabolism. Drug Metab. Rev., 2013, 45(1), 60-72.
[http://dx.doi.org/10.3109/03602532.2012.746363] [PMID: 23330542]
[186]
Flora, G.D.; Sahli, K.A.; Sasikumar, P.; Holbrook, L.M.; Stainer, A.R.; AlOuda, S.K.; Crescente, M.; Sage, T.; Unsworth, A.J.; Gibbins, J.M. Non-genomic effects of the pregnane X receptor negatively regulate platelet functions, thrombosis and haemostasis. Sci. Rep., 2019, 9(1), 17210.
[http://dx.doi.org/10.1038/s41598-019-53218-x] [PMID: 31748641]
[187]
Burk, O.; Kuzikov, M.; Kronenberger, T.; Jeske, J.; Keminer, O.; Thasler, W.E.; Schwab, M.; Wrenger, C.; Windshügel, B. Identification of approved drugs as potent inhibitors of pregnane X receptor activation with differential receptor interaction profiles. Arch. Toxicol., 2018, 92(4), 1435-1451.
[http://dx.doi.org/10.1007/s00204-018-2165-4] [PMID: 29356861]
[188]
Grewal, G.K.; Singh, K.D.; Kanojia, N.; Rawat, C.; Kukal, S.; Jajodia, A.; Singhal, A.; Misra, R.; Nagamani, S.; Muthusamy, K.; Kukreti, R. Exploring the carbamazepine interaction with human pregnane x receptor and effect on ABCC2 using in vitro and in silico approach. Pharm. Res., 2017, 34(7), 1444-1458.
[http://dx.doi.org/10.1007/s11095-017-2161-z] [PMID: 28432535]
[189]
Luo, G.; Cunningham, M.; Kim, S.; Burn, T.; Lin, J.; Sinz, M.; Hamilton, G.; Rizzo, C.; Jolley, S.; Gilbert, D.; Downey, A.; Mudra, D.; Graham, R.; Carroll, K.; Xie, J.; Madan, A.; Parkinson, A.; Christ, D.; Selling, B.; LeCluyse, E.; Gan, L.S. CYP3A4 induction by drugs: Correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes. Drug Metab. Dispos., 2002, 30(7), 795-804.
[http://dx.doi.org/10.1124/dmd.30.7.795] [PMID: 12065438]
[190]
Husain, I.; Dale, O.R.; Martin, K.; Gurley, B.J.; Adams, S.J.; Avula, B.; Chittiboyina, A.G.; Khan, I.A.; Khan, S.I. Screening of medicinal plants for possible herb-drug interactions through modulating nuclear receptors, drug-metabolizing enzymes and transporters. J. Ethnopharmacol., 2023, 301, 115822.
[http://dx.doi.org/10.1016/j.jep.2022.115822] [PMID: 36223846]
[191]
Liang, H.; Yang, X.; Li, H.; Wang, X.; Su, H.; Li, X.; Tian, J.; Cai, C.; Huang, M.; Bi, H. Schisandrol B protects against cholestatic liver injury by inhibiting pyroptosis through pregnane X receptor. Biochem. Pharmacol., 2022, 204, 115222.
[http://dx.doi.org/10.1016/j.bcp.2022.115222] [PMID: 35988735]
[192]
Zhou, C.; Poulton, E.J.; Grün, F.; Bammler, T.K.; Blumberg, B.; Thummel, K.E.; Eaton, D.L. The dietary isothiocyanate sulforaphane is an antagonist of the human steroid and xenobiotic nuclear receptor. Mol. Pharmacol., 2007, 71(1), 220-229.
[http://dx.doi.org/10.1124/mol.106.029264] [PMID: 17028159]
[193]
Alhusban, M.; Pandey, P.; Ahn, J.; Avula, B.; Haider, S.; Avonto, C.; Ali, Z.; Khan, S.I.; Ferreira, D.; Khan, I.A.; Chittiboyina, A.G. Computational tools to expedite the identification of potential PXR modulators in complex natural product mixtures: A case study with five closely related licorice species. ACS Omega, 2022, 7(30), 26824-26843.
[http://dx.doi.org/10.1021/acsomega.2c03240] [PMID: 35936409]
[194]
Wang, H.; Li, H.; Moore, L.B.; Johnson, M.D.L.; Maglich, J.M.; Goodwin, B.; Ittoop, O.R.R.; Wisely, B.; Creech, K.; Parks, D.J.; Collins, J.L.; Willson, T.M.; Kalpana, G.V.; Venkatesh, M.; Xie, W.; Cho, S.Y.; Roboz, J.; Redinbo, M.; Moore, J.T.; Mani, S. The phytoestrogen coumestrol is a naturally occurring antagonist of the human pregnane X receptor. Mol. Endocrinol., 2008, 22(4), 838-857.
[http://dx.doi.org/10.1210/me.2007-0218] [PMID: 18096694]
[195]
Wang, L.; Li, F.; Lu, J.; Li, G.; Li, D.; Zhong, X.; Guo, G.L.; Ma, X. The Chinese herbal medicine Sophora flavescens activates pregnane X receptor. Drug Metab. Dispos., 2010, 38(12), 2226-2231.
[http://dx.doi.org/10.1124/dmd.110.035253] [PMID: 20736322]
[196]
Lim, Y.P.; Ma, C.Y.; Liu, C.L.; Lin, Y.H.; Hu, M.L.; Chen, J.J.; Hung, D.Z.; Hsieh, W.T.; Huang, J.D. Sesamin: A naturally occurring lignan inhibits CYP3A4 by antagonizing the pregnane X receptor activation. Evid. Based Complement. Alternat. Med., 2012, 2012, 1-15.
[http://dx.doi.org/10.1155/2012/242810] [PMID: 22645625]
[197]
He, J.; Nishida, S.; Xu, M.; Makishima, M.; Xie, W. PXR prevents cholesterol gallstone disease by regulating biosynthesis and transport of bile salts. Gastroenterology, 2011, 140(7), 2095-2106.
[http://dx.doi.org/10.1053/j.gastro.2011.02.055] [PMID: 21354151]
[198]
Mooiman, K.D.; Maas-Bakker, R.F.; Moret, E.E.; Beijnen, J.H.; Schellens, J.H.M.; Meijerman, I. Milk thistle’s active components silybin and isosilybin: Novel inhibitors of PXR-mediated CYP3A4 induction. Drug Metab. Dispos., 2013, 41(8), 1494-1504.
[http://dx.doi.org/10.1124/dmd.113.050971] [PMID: 23674609]
[199]
Wang, C.; Huo, X.K.; Luan, Z.L.; Cao, F.; Tian, X.G.; Zhao, X.Y.; Sun, C.P.; Feng, L.; Ning, J.; Zhang, B.J.; Ma, X.C. Alismanin A, a triterpenoid with a C 34 skeleton from alisma orientale as a natural agonist of human pregnane X receptor. Org. Lett., 2017, 19(20), 5645-5648.
[http://dx.doi.org/10.1021/acs.orglett.7b02738] [PMID: 29016144]
[200]
Synold, T.W.; Dussault, I.; Forman, B.M. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat. Med., 2001, 7(5), 584-590.
[http://dx.doi.org/10.1038/87912] [PMID: 11329060]
[201]
Tabb, M.M.; Kholodovych, V.; Grün, F.; Zhou, C.; Welsh, W.J.; Blumberg, B. Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR). Environ. Health Perspect., 2004, 112(2), 163-169.
[http://dx.doi.org/10.1289/ehp.6560] [PMID: 14754570]
[202]
Sui, Y.; Meng, Z.; Chen, J.; Liu, J.; Hernandez, R.; Gonzales, M.B.; Gwag, T.; Morris, A.J.; Zhou, C. Effects of dicyclohexyl phthalate exposure on PXR activation and lipid homeostasis in mice. Environ. Health Perspect., 2021, 129(12), 127001.
[http://dx.doi.org/10.1289/EHP9262] [PMID: 34851150]
[203]
Attema, B.; Janssen, A.W.F.; Rijkers, D.; van Schothorst, E.M.; Hooiveld, G.J.E.J.; Kersten, S. Exposure to low-dose perfluorooctanoic acid promotes hepatic steatosis and disrupts the hepatic transcriptome in mice. Mol. Metab., 2022, 66, 101602.
[http://dx.doi.org/10.1016/j.molmet.2022.101602] [PMID: 36115532]
[204]
Lin, W.; Wang, Y.M.; Chai, S.C.; Lv, L.; Zheng, J.; Wu, J.; Zhang, Q.; Wang, Y.D.; Griffin, P.R.; Chen, T. SPA70 is a potent antagonist of human pregnane X receptor. Nat. Commun., 2017, 8(1), 741.
[http://dx.doi.org/10.1038/s41467-017-00780-5] [PMID: 28963450]
[205]
He, L.; Li, Y.; Zeng, N.; Stiles, B.L. Regulation of basal expression of hepatic PEPCK and G6Pase by AKT2. Biochem. J., 2020, 477(5), 1021-1031.
[http://dx.doi.org/10.1042/BCJ20190570] [PMID: 32096546]
[206]
Zhao, L.Y.; Xu, J.Y.; Shi, Z.; Englert, N.A.; Zhang, S.Y. Pregnane X receptor (PXR) deficiency improves high fat diet-induced obesity via induction of fibroblast growth factor 15 (FGF15) expression. Biochem. Pharmacol., 2017, 142, 194-203.
[http://dx.doi.org/10.1016/j.bcp.2017.07.019] [PMID: 28756207]

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