Farnesoid X receptor antagonizes nuclear factor κB in hepatic inflammatory response
Open accessAbstract
The farnesoid X receptor (FXR) is a nuclear receptor that plays key roles in hepatoprotection by maintaining the homeostasis of liver metabolism. FXR null mice display strong hepatic inflammation and develop spontaneous liver tumors. In this report, we demonstrate that FXR is a negative modulator of nuclear factor κB (NF-κB)–mediated hepatic inflammation. Activation of FXR by its agonist ligands inhibited the expression of inflammatory mediators in response to NF-κB activation in both HepG2 cells and primary hepatocytes cultured in vitro . In vivo , compared with wild-type controls, FXR−/− mice displayed elevated messenger RNA (mRNA) levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interferon-inducible protein 10, and interferon-γ in response to lipopolysaccharide (LPS). Examination of FXR−/− livers showed massive necroses and inflammation after treatment with LPS at a dose that does not induce significant liver damage or inflammation in wild-type mice. Moreover, transfection of a constitutively active FXR expression construct repressed the iNOS, COX-2, interferon-inducible protein 10 and interferon-γ mRNA levels induced by LPS administration. FXR activation had no negative effects on NF-κB-activated antiapoptotic genes, suggesting that FXR selectively inhibits the NF-κB-mediated hepatic inflammatory response but maintains or even enhances the cell survival response. On the other hand, NF-κB activation suppressed FXR-mediated gene expression both in vitro and in vivo , indicating a negative crosstalk between the FXR and NF-κB signaling pathways. Our findings reveal that FXR is a negative mediator of hepatic inflammation, which may contribute to the critical roles of FXR in hepatoprotection and suppression of hepatocarcinogenesis. (Hepatology 2008;48:1632–1643.)
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FXR agonists are known to alleviate endoplasmic reticulum stress and suppress oxidative damage by upregulating antioxidant and anti-apoptotic pathways.
“FXR agonists are known to alleviate endoplasmic reticulum stress and suppress oxidative damage by upregulating antioxidant and anti-apoptotic pathways [42, 43].”
From High-throughput human microfluidic organoid-on-a-chip platform for modeling liver diseases and screening nanotherapeutics. (2026) · cites this paper as [43]
The Results section on NF-κB-regulated pro-inflammatory genes reports that FXR agonists reduce inflammatory gene expression, not endoplasmic reticulum stress or oxidative damage. The Results section on anti-apoptosis target genes says FXR activation did not suppress those genes; it does not establish their upregulation. Searches for endoplasmic reticulum stress, oxidative damage, and antioxidant pathways found no passage addressing the claimed mechanism. (LLM, conf=0.75)
Experimental — accuracy not yet measuredAblation of Fxr promotes cholestasis, NAFLD, NASH and HCC in mice.
“Ablation of Nr1h4 (hereafter referred to as Fxr) not only promotes cholestasis but also NAFLD, NASH and HCC in mice (Kim et al., 2007; Lu et al., 2000; Wang et al., 2008; Watanabe et al., 2004; Yang et al., 2007).”
From Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis (2016) · cites this paper as Wang et al., 2008
Nuclear receptors are able to mediate anti-inflammatory effects through direct interaction with other transcription factors such as NF-κB or AP-1, and can repress proinflammatory gene expression by interfering with TLR signaling.
“Next to their extensive effect on cell metabolism, they are able to mediate anti-inflammatory effects through direct interaction with other transcription factors, such as NF-κB or activator protein-1 (AP-1) [26,27], and even repress proinflammatory gene expression by interfering with TLR signaling.[28]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [27]
FXR interacts with NF-κB signaling and inhibits pro-inflammatory genes such as TNF-α, iNOS, COX-2, CCL-2 and IL-1β, while NF-κB activation reciprocally antagonizes FXR activity.
“In brief, FXR interacts with NF-κB signaling and inhibits pro-inflammatory genes (e.g., TNF-α, inducible nitric oxide synthase (iNOS), Cyclooxygeanse-2 (COX-2), CCL-2 and IL-1β)), while NF-κB activation reciprocally antagonizes FXR activity.[27,52,53]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [27]
FXR -/- mice were more susceptible to inflammatory stress, highlighting the anti-inflammatory properties of FXR.
“Additionally, FXR -/-mice were more susceptible to inflammatory stress, highlighting the anti- inflammatory properties of FXR.[27]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [27]
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Cites
The nuclear receptor superfamily: the second decade
Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90199-x · Cited by 6,964 · see citing works
NF-κB: linking inflammation and immunity to cancer development and progression
Karin, M., & Greten, F. R. (2005) · Nature reviews. Immunology · doi:10.1038/nri1703 · Cited by 3,091 · see citing works
Wang, C.-Y., Mayo, M., Korneluk, R., Goeddel, D., & Baldwin, A. (1998) · Science · doi:10.1126/science.281.5383.1680 · Cited by 2,950 · see citing works
IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer
Greten, F. R., Eckmann, L., Greten, T. F., Park, J. M., Li, Z.-W., Egan, L. J., Kagnoff, M. F., & Karin, M. (2004) · Cell · doi:10.1016/j.cell.2004.07.013 · Cited by 2,433 · see citing works
NF-κB functions as a tumour promoter in inflammation-associated cancer
Pikarsky, E., Porat, R., Stein, I., Abramovitch, R., Amit, S., Kasem, S., Gutkovich-Pyest, E., Urieli-Shoval, S., Galun, E., & Ben-Neriah, Y. (2004) · Nature · doi:10.1038/nature02924 · Cited by 2,295 · see citing works
Gender Disparity in Liver Cancer Due to Sex Differences in MyD88-Dependent IL-6 Production
Naugler, W. E., Sakurai, T., Kim, S., Maeda, S., Kim, K., Elsharkawy, A. M., & Karin, M. (2007) · Science · doi:10.1126/science.1140485 · Cited by 1,955 · see citing works
Targeted 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
Self-citationNuclear factor-κB: The enemy within
Aggarwal, B. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.09.003 · Cited by 1,289 · see citing works
A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ
Pascual, G., Fong, A. L., Ogawa, S., Gamliel, A., Li, A. C., Perissi, V., Rose, D. W., Willson, T. M., Rosenfeld, M. G., & Glass, C. K. (2005) · Nature · doi:10.1038/nature03988 · Cited by 1,251 · see citing works
Reciprocal regulation of inflammation and lipid metabolism by liver X receptors
Joseph, S. B., Castrillo, A., Laffitte, B. A., Mangelsdorf, D. J., & Tontonoz, P. (2003) · Nature Medicine · doi:10.1038/nm820 · Cited by 1,158 · see citing works
Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice
Zhang, Y., Lee, F. Y., Barrera, G., Lee, H., Vales, C., Gonzalez, F. J., Willson, T. M., & Edwards, P. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506982103 · Cited by 961 · see citing works
To be, or not to be: NF-κB is the answer – role of Rel/NF-κB in the regulation of apoptosis
Kucharczak, J., Simmons, M. J., Fan, Y., & Gélinas, C. (2003) · Oncogene · doi:10.1038/sj.onc.1207230 · Cited by 761 · see citing works
Zong, W.-X., Edelstein, L., Chen, C.-L., Bash, J., & Gélinas, C. (1999) · Genes & Development · doi:10.1101/gad.13.4.382 · Cited by 738 · see citing works
Molecular determinants of crosstalk between nuclear receptors and toll-like receptors
Ogawa, S., Lozach, J., Benner, C., Pascual, G., Tangirala, R. K., Westin, S., Hoffmann, A., Subramaniam, S., David, M., Rosenfeld, M. G., et al. (2005) · Cell · doi:10.1016/j.cell.2005.06.029 · Cited by 647 · see citing works
Nuclear Receptor-Dependent Bile Acid Signaling Is Required for Normal Liver Regeneration
Huang, W., Ma, K., Zhang, J., Qatanani, M., Cuvillier, J., Liu, J., Dong, B., Huang, X., & Moore, D. D. (2006) · Science · doi:10.1126/science.1121435 · Cited by 645 · see citing works
Self-citationKim, I., Ahn, S.-H., Inagaki, T., Choi, M., Ito, S., Guo, G. L., Kliewer, S., & Gonzalez, F. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700330-jlr200 · Cited by 575 · see citing works
Ghisletti, S., Huang, W., Ogawa, S., Pascual, G., Lin, M.-E., Willson, T. M., Rosenfeld, M. G., & Glass, C. K. (2007) · Molecular Cell · doi:10.1016/j.molcel.2006.11.022 · Cited by 561 · see citing works
Self-citationNissen, R. M., & Yamamoto, K. R. (2000) · Genes & Development · doi:10.1101/gad.827900 · Cited by 559 · see citing works
Yang, F., Huang, X., Yi, T., Yen, Y., Moore, D. D., & Huang, W. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-1078 · Cited by 488 · see citing works
Self-citationZhou, C. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26283 · Cited by 401 · see citing works
Self-citationNuclear factor‐κB and the hepatic inflammation‐fibrosis‐cancer axis†
Elsharkawy, A. M., & Mann, D. A. (2007) · Hepatology · doi:10.1002/hep.21802 · Cited by 400 · 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
Ricote, M., Huang, J. T., Welch, J., & Glass, C. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.66.5.733 · Cited by 392 · see citing works
Neutrophils aggravate acute liver injury during obstructive cholestasis in bile duct–ligated mice
Gujral, J., Farhood, A., Bajt, M., & Jaeschke, H. (2003) · Hepatology · doi:10.1053/jhep.2003.50341 · Cited by 353 · see citing works
Prevention of cholesterol gallstone disease by FXR agonists in a mouse model
Moschetta, A., Bookout, A. L., & Mangelsdorf, D. J. (2004) · Nature Medicine · doi:10.1038/nm1138 · Cited by 326 · see citing works
Role of NF-κB in Regulation of PXR-mediated Gene Expression
Gu, X., Ke, S., Liu, D., Sheng, T., Thomas, P. E., Rabson, A. B., Gallo, M. A., Xie, W., & Tian, Y. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601302200 · Cited by 311 · see citing works
Qiao, L., Studer, E., Leach, K., McKinstry, R., Gupta, S., Decker, R., Kukreja, R., Valerie, K., Nagarkatti, P., El-Deiry, W., et al. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.9.2629 · Cited by 242 · see citing works
Urizar, N. L., Dowhan, D. H., & Moore, D. D. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m007998200 · Cited by 238 · see citing works
Cross-talk between glucocorticoid receptor and AP-1
Herrlich, P. A. (2001) · Oncogene · doi:10.1038/sj.onc.1204388 · Cited by 229 · see citing works
A traditional herbal medicine enhances bilirubin clearance by activating the nuclear receptor CAR.
Huang, W.-D., Zhang, J., & Moore, D. (2004) · Journal of Clinical Investigation · doi:10.1172/jci18385 · Cited by 224 · see citing works
Self-citationKe, S., Rabson, A., Germino, J., Gallo, M., & Tian, Y.-N. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106286200 · Cited by 217 · see citing works
Baek, J., Jang, J.-E., Kang, C., Chung, H., Kim, N., & Kim, K.-W. (2000) · Oncogene · doi:10.1038/sj.onc.1203814 · Cited by 196 · see citing works
Li, M. K., & Crawford, J. (2004) · Seminars in liver disease (Print) · doi:10.1055/s-2004-823099 · Cited by 173 · see citing works
Farnesoid x receptor ligands inhibit vascular smooth muscle cell inflammation and migration
Li, Y. T. Y., Swales, K. E., Thomas, G. J., Warner, T. D., & Bishop-Bailey, D. (2007) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.152694 · Cited by 171 · see citing works
AP-1--glucocorticoid receptor crosstalk taken to a higher level
Karin, M., & Chang, L. (2001) · Journal of Endocrinology · doi:10.1677/joe.0.1690447 · Cited by 167 · see citing works
Repression of Farnesoid X Receptor during the Acute Phase Response
Kim, M. S., Shigenaga, J. K., Moser, A., Feingold, K. R., & Grünfeld, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212633200 · Cited by 151 · see citing works
Inflammation and Cancer. I. Rodent models of infectious gastrointestinal and liver cancer.
Rogers, A., & Fox, J. (2004) · American Journal of Physiology - Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00499.2003 · Cited by 137 · see citing works
Jenkins, G., Harries, K., Doak, S., Wilmes, A., Griffiths, A., Baxter, J., & Parry, J. (2003) · Carcinogenesis · doi:10.1093/carcin/bgh032 · Cited by 135 · see citing works
Huang, W., Zhang, J., Wei, P., Schrader, W. T., & Moore, D. D. (2004) · Molecular Endocrinology · doi:10.1210/me.2004-0046 · Cited by 110 · see citing works
Self-citationShah, S. T. A., Volkov, Y., Arfin, Q., Abdel-Latif, M. M. M., & Kelleher, D. (2006) · International Journal of Cancer · doi:10.1002/ijc.21365 · Cited by 76 · see citing works
Liver Receptor Homolog 1 Is a Negative Regulator of the Hepatic Acute-Phase Response
Venteclef, N., Smith, J. C., Goodwin, B., & Delerive, P. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00579-06 · Cited by 70 · see citing works
Wang, Y.-D., Yang, F., Chen, W.-D., Huang, X.-F., Lai, L., Forman, B. M., & Huang, W.-D. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0527 · Cited by 61 · see citing works
Self-citationLiver X receptor-alpha gene expression is positively regulated by thyroid hormone.
Hashimoto, K., Matsumoto, S., Yamada, M., Satoh, T., & Mori, M. (2007) · Endocrinology · doi:10.1210/en.2007-0150 · Cited by 60 · see citing works
FXR, a target for different diseases.
Wang, Y.-D., Chen, W.-D., & Huang, W.-D. (2008) · Histology and Histopathology · doi:10.14670/hh-23.621 · Cited by 57 · see citing works
Self-citationNajima, Y., Yahagi, N., Takeuchi, Y., Matsuzaka, T., Sekiya, M., Nakagawa, Y., Amemiya-Kudo, M., Okazaki, H., Okazaki, S., Tamura, Y., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414549200 · Cited by 47 · see citing works
Specific Protein-1 Is a Universal Regulator of UDP-glucose Dehydrogenase Expression
Bontemps, Y., Vuillermoz, B., Antonicelli, F., Perreau, C., Danan, J., Maquart, F., & Wegrowski, Y. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209366200 · Cited by 47 · see citing works
Najima, Y., Yahagi, N., Takeuchi, Y., Matsuzaka, T., Sekiya, M., Nakagawa, Y., Amemiya-Kudo, M., Okazaki, H., Okazaki, S., Tamura, Y., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414549200\|[sect · Cited by 30
Wang, L., Zhang, X., Farrar, W. L., & Yang, X. (2004) · PubMed · Cited by 19 · see citing works
Flagged first, then by citations
3 of the 52 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis
Jia, W., Xie, G., & Jia, W. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.119 · Cited by 1,924 · see citing works
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529 · see citing works
Bile Acid Metabolism and Signaling
Chiang, J. Y. L. (2013) · Comprehensive physiology · doi:10.1002/j.2040-4603.2013.tb00517.x · Cited by 286 · 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
“Stimulation of FXR in isolated hepatocytes and HepG2 hepatoma cells significantly suppressed NF-kappaB transcriptional activity (Wang et al. 2008a).”
Younossi, Z. M., Ratziu, V., Loomba, R., Rinella, M., Anstee, Q. M., Goodman, Z., Bedossa, P., Geier, A., Beckebaum, S., Newsome, P. N., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)33041-7 · Cited by 1,277 · see citing works
Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives
Roehlen, N., Crouchet, E., & Baumert, T. F. (2020) · Cells · doi:10.3390/cells9040875 · Cited by 1,237 · 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
“OCA antagonizes NF-kB–stimulated inflammation in liver (Wang et al., 2008), modulates innate immunity in animal models of colitis (Vavassori et al.”
BackgroundInfluentialMudaliar, S., Henry, R. R., Sanyal, A. J., Morrow, L., Marschall, H., Kipnes, M., Adorini, L., Sciacca, C. I., Clopton, P., Castelloe, E., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.05.042 · Cited by 931 · see citing works
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876 · see citing works
Gadaleta, R. M., van Erpecum, K. J., Oldenburg, B., Willemsen, E. C. L., Renooij, W., Murzilli, S., Klomp, L. W. J., Siersema, P. D., Schipper, M. E. I., Danese, S., et al. (2011) · Gut · doi:10.1136/gut.2010.212159 · Cited by 870 · see citing works
Hepatic inflammatory responses in liver fibrosis
Hammerich, L., & Tacke, F. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00807-x · Cited by 803 · see citing works
“By contrast, activation of the nuclear receptor farnesoid X receptor (FXR) in hepatocytes by distinct (endogenous or synthetic) bile acids prevents the upregulation of inflammatory response genes and promotes cell survival 34 .”
Dietary metabolism, the gut microbiome, and heart failure
Tang, W. H. W., Li, D. Y., & Hazen, S. L. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0108-7 · Cited by 789 · see citing works
Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum
Hardy, T., Oakley, F., Anstee, Q. M., & Day, C. P. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044224 · Cited by 619 · see citing works
“LPS is delivered directly to the liver via the portal vein and is recognized by TLR4 located on Kupffer cells, the resident hepatic macrophages; activation of TLR4 by LPS requires coreceptors CD14 and MD-2 and results in activation of myeloid differentiation factor 88 (MyD88)– dependent and Toll/interleukin-1 receptor…”
BackgroundInfluentialFleishman, J. S., & Kumar, S. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01811-6 · Cited by 577 · see citing works
Circadian Homeostasis of Liver Metabolism Suppresses Hepatocarcinogenesis
Kettner, N. M., Voicu, H., Finegold, M. J., Coarfa, C., Sreekumar, A., Putluri, N., Katchy, C. A., Lee, C., Moore, D. D., & Fu, L. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.10.007 · Cited by 508 · see citing works
“Ablation of Nr1h4 (hereafter referred to as Fxr) not only promotes cholestasis but also NAFLD, NASH and HCC in mice (Kim et al., 2007; Lu et al., 2000; Wang et al., 2008; Watanabe et al., 2004; Yang et al., 2007).”
BackgroundRole of bile acids and their receptors in gastrointestinal and hepatic pathophysiology
Fuchs, C. D., & Trauner, M. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00566-7 · Cited by 490 · 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
Non-alcoholic steatohepatitis: emerging molecular targets and therapeutic strategies
Musso, G., Cassader, M., & Gambino, R. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2015.3 · Cited by 415 · see citing works
Bile Acid Metabolism in Liver Pathobiology
Chiang, J. Y. L., & Ferrell, J. M. (2018) · Gene Expression · doi:10.3727/105221618x15156018385515 · Cited by 552 · see citing works
Wang, Y., Chen, W., Yu, D. D., FORMAN, B. M., & Huang, W. (2011) · Hepatology · doi:10.1002/hep.24525 · Cited by 488 · see citing works
Self-citationGut Microbiota: An Integral Moderator in Health and Disease
Feng, Q., Chen, W.-D., & Wang, Y.-D. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00151 · Cited by 407 · see citing works
“FXR plays a pivotal role in host liver metabolism, including liver regeneration, hepatoprotection, prevention of NAFLD and hepatocarcinogenesis (Wang et al., 2008a,b; Chiang, 2013; Zhang et al., 2016).”
BackgroundSelf-citationThe immunobiology and pathophysiology of primary biliary cirrhosis
Hirschfield, G. M., & Gershwin, M. E. (2013) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-164014 · Cited by 315 · see citing works
“A specific example is farnesoid X receptors (FXRs); data support a role for the bile acid sensor FXR in the regulation of liver NKT cell activation, and FXR may also be a negative modulator of NFκB-mediated hepatic inflammation (142, 143).”
BackgroundZhang, S., Wang, J., Liu, Q., & Harnish, D. C. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.03.025 · Cited by 290 · see citing works
Pathogenesis of cholestatic liver disease and therapeutic approaches
Hirschfield, G. M., Heathcote, E. J., & Gershwin, M. E. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.09.004 · Cited by 287 · see citing works
Bile Acid Metabolism and Signaling in Cholestasis, Inflammation, and Cancer
Li, T., & Apte, U. M. (2015) · Advances in pharmacology · doi:10.1016/bs.apha.2015.04.003 · Cited by 335 · see citing works
“Fxr knockout mice showed increased liver inflammation, while FXR activation decreased lipopolysaccharide (LPS)induced hepatic inflammation (Wang et al., 2008).”
BackgroundNew molecular insights into the mechanisms of cholestasis.
Wagner, M., Zollner, G., & Trauner, M. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.05.012 · Cited by 270 · see citing works
“Pro-inflammatory cytokines are potent inhibitors of hepatobiliary transport and NR expression and function [2,145,146].”
BackgroundEmerging roles of bile acids in mucosal immunity and inflammation
Chen, M. L., Takeda, K., & Sundrud, M. S. (2019) · Mucosal Immunology · doi:10.1038/s41385-019-0162-4 · Cited by 301 · see citing works
Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression
Caligiuri, A., Gentilini, A., Pastore, M., Gitto, S., & Marra, F. (2021) · Cells · doi:10.3390/cells10102759 · Cited by 273 · see citing works
Current efforts and trends in the treatment of NASH
Ratziu, V., Goodman, Z. D., & Sanyal, A. J. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.041 · Cited by 263 · see citing works
“Interestingly, FXR activation has also anti-inflammatory actions [116,117] with resultant protection against liver inflammation and fibrosis in the methionine/choline deficient model of NASH [118].”
BackgroundFarnesoid X receptor targeting to treat nonalcoholic steatohepatitis
Adorini, L., Pruzanski, M., & Shapiro, D. (2012) · Drug Discovery Today · doi:10.1016/j.drudis.2012.05.012 · Cited by 259 · see citing works
Verbeke, L., Farre, R., Trebicka, J., Komuta, M., Roskams, T., Klein, S., Elst, I. V., Windmolders, P., Vanuytsel, T., Nevens, F., et al. (2014) · Hepatology · doi:10.1002/hep.26939 · Cited by 258 · see citing works
“Besides its considered traditional function as a chief regulator of bile acid homeostasis, the FXR system has also been implicated in other physiological events, including regulation of lipid and carbohydrate metabolism, liver repair, and hepatoprotection.(23,24,27,40,41) As a result, FXR dysfunction has been suggeste…”
BackgroundDysregulated hepatic bile acids collaboratively promote liver carcinogenesis
Xie, G., Wang, X., Huang, F., Zhao, A., Chen, W., Yan, J., Zhang, Y., Lei, S., Ge, K., Zheng, X., et al. (2016) · International Journal of Cancer · doi:10.1002/ijc.30219 · Cited by 252 · see citing works
Self-citationBishehsari, F. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i20.6055 · Cited by 266 · see citing works
The role of bile acids in carcinogenesis
Režen, T., Rozman, D., Kovàcs, T., Kovács, P., Sipos, A., Bai, P., & Mikó, E. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04278-2 · Cited by 299 · see citing works
Verbeke, L., Mannaerts, I., Schierwagen, R., Govaere, O., Klein, S., Vander Elst, I., Windmolders, P., Farre, R., Wenes, M., Mazzone, M., et al. (2016) · Scientific Reports · doi:10.1038/srep33453 · Cited by 236 · see citing works
TGR5, Not Only a Metabolic Regulator
Guo, C., Chen, W.-D., & Wang, Y.-D. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00646 · Cited by 231 · see citing works
“CDCA, DCA, LCA, ursodeoxycholic acid (UDCA) are not only the activators of TGR5 but also the activators of farnesoid X receptor (FXR) (Makishima et al., 1999; Wang et al., 2008a,b).”
BackgroundInfluentialSelf-citationNew therapeutic concepts in bile acid transport and signaling for management of cholestasis
Trauner, M., Fuchs, C. D., Halilbasic, E., & Paumgartner, G. (2017) · Hepatology · doi:10.1002/hep.28991 · Cited by 227 · see citing works
“ed to possible role in pruritus,((17)) gallbladder distension,((18,19)) and”
McMahan, R. H., Wang, X. X., Cheng, L. L., Krisko, T., Smith, M., El Kasmi, K., Pruzanski, M., Adorini, L., Golden-Mason, L., Levi, M., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.446575 · Cited by 225 · see citing works
“Furthermore, FXR exerts homoeostatic functions at the interface between nutrient and lipid metabolism with innate immunity, antagonizing NF- B in hepatic inflammatory responses (17) and inhibiting intestinal inflammatory responses (16, 18).”
BackgroundVerbeke, L., Farre, R., Verbinnen, B., Covens, K., Vanuytsel, T., Verhaegen, J., Komuta, M., Roskams, T., Chatterjee, S., Annaert, P., et al. (2015) · The American Journal of Pathology · doi:10.1016/j.ajpath.2014.10.009 · Cited by 225 · see citing works
Poupon, R. Y. (2012) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/s2210-7401(12)70015-3 · Cited by 224 · see citing works
The Spectrum of Achalasia: Lessons From Studies of Pathophysiology and High-Resolution Manometry
Kahrilas, P. J., & Boeckxstaens, G. E. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.08.038 · Cited by 234 · see citing works
Novel therapeutic targets for cholestatic and fatty liver disease
Trauner, M., & Fuchs, C. D. (2022) · Gut · doi:10.1136/gutjnl-2021-324305 · Cited by 204 · see citing works
Bile acid metabolism and signalling in liver disease
Fuchs, C. D., Simbrunner, B., Baumgartner, M., Campbell, C., Reiberger, T., & Trauner, M. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.09.032 · Cited by 246 · see citing works
Kasmi, K. E., Anderson, A. L., Devereaux, M., Vue, P. M., Zhang, W.-J., Setchell, K., Karpen, S., & Sokol, R. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006898 · Cited by 201 · see citing works
Gadaleta, R. M., Oldenburg, B., Willemsen, E. C. L., Spit, M., Murzilli, S., Salvatore, L., Klomp, L. W. J., Siersema, P. D., van Erpecum, K. J., & van Mil, S. W. C. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.04.005 · Cited by 195 · see citing works
“N [10] Also, FXR-mediated gene expression was shown to be suppressed during hepatic inflammation[11] and FXR mRNA expression was shown to be reduced in inflamed colonic mucosa in a small cohort of Crohn’s patients.”
BackgroundRizzo, G., Passeri, D., Franco, F., Ciaccioli, G., Donadio, L., Rizzo, G., Orlandi, S., Sadeghpour, B. M., Wang, X. X., Jiang, T., et al. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.064501 · Cited by 198 · see citing works
“INT-747 also shows antifibrotic (Fiorucci et al., 2004; Wang et al., 2009) and anti-inflammatory (Wang et al., 2008) properties and modulates lipid (Rizzo et al., 2006) and glucose (Cipriani et al., 2009) metabolism.”
BackgroundBile Acids Activate YAP to Promote Liver Carcinogenesis
Anakk, S., Bhosale, M., Schmidt, V. A., Johnson, R. L., Finegold, M. J., & Moore, D. D. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.10.030 · Cited by 196 · see citing works
“Liver tumors occur in single Fxr / and Shp / mice at 15 months of age (Yang et al., 2007), and the underlying mechanism for tumor formation is either via elevated proinflammatory cascade (Wang et al., 2008) or by increased cellular proliferation (Zhang et al., 2008).”
Akkız, H., Gieseler, R. K., & Canbay, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147873 · Cited by 191 · see citing works
“Conversely, hepatocellular FXR activation by different bile acids prevents the upregulation of inflammatory response genes and induces cell survival [103].”
BackgroundFarnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis
Jiao, Y., Lu, Y., & Li, X.-Y. (2014) · Acta Pharmacologica Sinica · doi:10.1038/aps.2014.116 · Cited by 201 · see citing works
Crosstalk between bile acid-activated receptors and microbiome in entero-hepatic inflammation
Thibaut, M. M., & Bindels, L. B. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2021.12.006 · Cited by 187 · see citing works
Wang, X.-X. X., Jiang, T., Shen, Y., Caldas, Y. A., Miyazaki-anzai, S., Santamaria, H., Urbanek, C., Solis, N., Scherzer, P., Lewis, L., et al. (2010) · Diabetes · doi:10.2337/db10-0019 · Cited by 183 · see citing works
“In vascular smooth muscle cells (42), the counterpart of glomerular mesangial cells, and in hepatocytes (43), INT-747 has been shown to inhibit the inflammatory response by antagonizing the NF B signaling pathway.”
BackgroundResultΠέττα, Ι., Dejager, L., Ballegeer, M., Lievens, S., Tavernier, J. H., Bosscher, K. D., & Libert, C. (2016) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00064-15 · Cited by 202 · see citing works
Bile Acids and FXR: Novel Targets for Liver Diseases
Stofan, M., & Guo, G. L. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.00544 · Cited by 202 · see citing works
Schwabl, P., Hambruch, E., Seeland, B. A., Hayden, H., Wagner, M., Garnys, L., Strobel, B., Schubert, T.-L., Riedl, F., Mitteregger, D., et al. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2016.12.005 · Cited by 178 · see citing works
Fickert, P., Fuchsbichler, A., Moustafa, T., Wagner, M., Zollner, G., Halilbasic, E., Stöger, U., Arrese, M., Pizarro, M., Solís, N., et al. (2009) · The American Journal of Pathology · doi:10.2353/ajpath.2009.090114 · Cited by 169 · see citing works
“FXR / mice may be prone to development of infectioninduced liver fibrosis as a result of lacking FXR-mediated repression of hepatic inflammation.(40) We therefore compared the fibrotic response of S.”
BackgroundIvermectin: An Anthelmintic, an Insecticide, and Much More
Martin, R. J., Robertson, A., & Choudhary, S. (2020) · Trends in Parasitology · doi:10.1016/j.pt.2020.10.005 · Cited by 167
FXR agonists in NASH treatment
Adorini, L., & Trauner, M. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.07.034 · Cited by 197 · see citing works
Bile acids and their receptors
Martinot, E., Sèdes, L., Baptissart, M., Lobaccaro, J.-M., Caira, F., Beaudoin, C., & Volle, D. H. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.01.006 · Cited by 162 · see citing works
SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis
Zhou, J., Cui, S., He, Q., Guo, Y., Pan, X., Zhang, P., Huang, N., Ge, C., Wang, G., Gonzalez, F. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14138-6 · Cited by 154 · see citing works
The oral microbiome in the pathophysiology of cardiovascular disease
Tonelli, A., Lumngwena, E. N., & Ntusi, N. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00825-3 · Cited by 181 · see citing works
Sterol Regulation of Metabolism, Homeostasis, and Development
Wollam, J., & Antebi, A. (2011) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-081308-165917 · Cited by 169 · see citing works
Bile acids and their nuclear receptor FXR: Relevance for hepatobiliary and gastrointestinal disease
Gadaleta, R. M., van Mil, S. W. C., Oldenburg, B., Siersema, P. D., Klomp, L. W. J., & van Erpecum, K. J. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.04.006 · Cited by 147 · see citing works
Promotion of liver regeneration/repair by farnesoid X receptor in both liver and intestine in mice
Zhang, L., Wang, Y.-D., Chen, W.-D., Wang, X., Lou, G., Liu, N., Lin, M., Forman, B. M., & Huang, W. (2012) · Hepatology · doi:10.1002/hep.25905 · Cited by 151 · see citing works
Self-citationBile acids and bariatric surgery
Albaugh, V. L., Banan, B., Ajouz, H., Abumrad, N. N., & Flynn, C. R. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.04.001 · Cited by 148 · see citing works
“…et al., 2016) and inflammatory macrophage activation (Kawamata et al., 2003; Keitel et al., 2008; Lou et al., 2014; Maruyama et al., 2002; Y. D. Wang et al., 2008), improves pancreatic function (Kumar et al., 2016; Vettorazzi et al., 2016) and improves non-alcoholic fatty liver disease (Ding…”
BackgroundFXR in liver physiology: Multiple faces to regulate liver metabolism
Panzitt, K., & Wagner, M. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166133 · Cited by 160 · see citing works
Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?
Fukui, H. (2019) · Diseases · doi:10.3390/diseases7040058 · Cited by 151 · see citing works
Zhang, Y., Xu, Y.-W., Qi, Y., Xu, L.-N., Song, S., Yin, L., Tao, X.-F., Zhen, Y.-H., Han, X., Ma, X.-D., et al. (2017) · Toxicology · doi:10.1016/j.tox.2017.01.007 · Cited by 136 · see citing works
Baars, A., Oosting, A., Knol, J., Garssen, J., & Van Bergenhenegouwen, J. (2015) · Microorganisms · doi:10.3390/microorganisms3040641 · Cited by 135 · see citing works
Bile acids and their receptors: modulators and therapeutic targets in liver inflammation
Bertolini, A., Fiorotto, R., & Strazzabosco, M. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00935-7 · Cited by 142 · see citing works
Bhargava, P., Li, C., Stanya, K. J., Jacobi, D., Dai, L., Liu, S., Gangl, M. R., Harn, D. A., & Lee, C. (2012) · Nature Medicine · doi:10.1038/nm.2962 · Cited by 124 · see citing works
TGR5: A Novel Target for Weight Maintenance and Glucose Metabolism
Chen, X., Lou, G., Meng, Z., & Huang, W. (2011) · Experimental Diabetes Research · doi:10.1155/2011/853501 · Cited by 121 · see citing works
Self-citationA dysregulated acetyl/SUMO switch of FXR promotes hepatic inflammation in obesity
Kim, D., Xiao, Z., Kwon, S., Sun, X., Ryerson, D., Tkac, D., Ma, P., Wu, S., Chiang, C., Zhou, E., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201489527 · Cited by 126 · see citing works
“Agonist-activated FXR inhibited NF-jB target inflammatory genes in hepatocytes (Wang et al, 2008) and also acted as an important modulator of innate immunity in the intestine (Vavassori et al, 2009).”
BackgroundEDP-305 in patients with NASH: a phase II double-blind placebo-controlled dose-ranging study
Ratziu, V., Rinella, M. E., Neuschwander-Tetri, B. A., Lawitz, E., Denham, D., Kayali, Z., Sheikh, A., Kowdley, K. V., Desta, T., Elkhashab, M., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.10.018 · Cited by 123 · see citing works
Bile acid receptors in non-alcoholic fatty liver disease
Li, Y., Jadhav, K. S., & Zhang, Y. (2013) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.08.015 · Cited by 136 · see citing works
Nuclear Receptors as New Perspective for the Management of Liver Diseases
Trauner, M., & Halilbasic, E. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.02.044 · Cited by 114 · see citing works
Degirolamo, C., Modica, S., Vacca, M., Di Tullio, G., Morgano, A., D'Orazio, A., Kannisto, K., Parini, P., & Moschetta, A. (2015) · Hepatology · doi:10.1002/hep.27274 · Cited by 121 · see citing works
Farnesoid X receptor (FXR) activation and FXR genetic variation in inflammatory bowel disease
Nijmeijer, R. M., Gadaleta, R. M., van Mil, S. W. C., van Bodegraven, A. A., Crusius, J. B. A., Dijkstra, G., Hommes, D. W., de Jong, D. J., Stokkers, P. C. F., Verspaget, H. W., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023745 · Cited by 119 · see citing works
“Notably, we and others previously showed that there is reciprocal repression of FXR and NF-kB in vitro and in vivo [19,20].”
A mouse tissue transcription factor atlas
Zhou, Q., Liu, M., Xia, X., Gong, T., Feng, J., Liu, W., Liu, Y., Zhen, B., Wang, Y., Ding, C., et al. (2017) · Nature Communications · doi:10.1038/ncomms15089 · Cited by 119 · see citing works
Self-citationPi, Y., Wu, Y., Zhang, X., Lu, D., Han, D., Zhao, J., Zheng, X., Zhang, S., Ye, H., Lian, S., et al. (2023) · Microbiome · doi:10.1186/s40168-022-01458-x · Cited by 138 · see citing works
Obeticholic acid protects mice against lipopolysaccharide-induced liver injury and inflammation
Xiong, X., Ren, Y., Cui, Y., Li, R., Wang, C., & Zhang, Y. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.11.083 · Cited by 125 · see citing works
FXR Regulates Liver Repair after CCl4-Induced Toxic Injury
Meng, Z., Wang, Y., Wang, L., Jin, W., Liu, N., Pan, H., Liu, L., Wagman, L. D., FORMAN, B. M., & Huang, W. (2010) · Molecular Endocrinology · doi:10.1210/me.2009-0286 · Cited by 113 · see citing works
“RNA preparation was described previously (22).”
InfluentialSelf-citationChen, W.-D., Wang, Y.-D., Zhang, L., Shiah, S., Wang, M., Yang, F., Yu, D., Forman, B. M., & Huang, W. (2010) · Hepatology · doi:10.1002/hep.23390 · Cited by 115 · see citing works
Self-citationFatty liver diseases, bile acids, and FXR
Zhu, Y., Liu, H., Zhang, M., & Guo, G. L. (2016) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2016.07.008 · Cited by 118 · see citing works
Bile acid dysregulation, gut dysbiosis, and gastrointestinal cancer
Tsuei, J., Chau, T., Mills, D. A., & Wan, Y. Y. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214538743 · Cited by 118 · see citing works
“Moreover, FXR stimulation can down-regulate lipopolysaccharide (LPS)-induced, nuclear factor kappa-light-chainenhancer of activated B cells (NFkb)-mediated hepatic inflammation by suppressing the expression of proinflammatory mediators in human HCC cells and mouse primary hepatocytes.(33) FXR KO mice displayed higher…”
BackgroundFXR Agonists as Therapeutic Agents for Non-alcoholic Fatty Liver Disease
Carr, R. M., & Reid, A. E. (2015) · Current Atherosclerosis Reports · doi:10.1007/s11883-015-0500-2 · Cited by 125 · see citing works
Progress and challenges of selective Farnesoid X Receptor modulation
Massafra, V., Pellicciari, R., Gioiello, A., & van Mil, S. W. C. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.06.009 · Cited by 129 · see citing works
Nuclear bile acid signaling through the farnesoid X receptor
Mazuy, C., Helleboid, A., Staels, B., & Lefebvre, P. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1805-y · Cited by 111 · see citing works
“Conversely, NF-kappaB represses FXR activity in liver and intestinal cells [210, 212].”
BackgroundWu, W., Zhu, B., Peng, X., Zhou, M.-L., Jia, D., & Gu, J.-X. (2014) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2013.11.057 · Cited by 111 · see citing works
Claudel, T., Zollner, G., Wagner, M., & Trauner, M. A. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.12.021 · Cited by 101 · see citing works
The role of bile acids in cholestatic liver injury
Cai, S.-Y., & Boyer, J. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-5110 · Cited by 110 · see citing works
“In contrast, a few studies indicate that activation of FXR mitigates hepatic inflammation by inhibiting NFkB signaling pathway (16-18).”
BackgroundLiu, N., Meng, Z., Lou, G., Zhou, W., Wang, X., Zhang, Y., Zhang, L., Liu, X., Yen, Y., Lai, L. L., et al. (2012) · Molecular Endocrinology · doi:10.1210/me.2011-1383 · Cited by 109 · see citing works
Self-citationYu, J., Zheng, J.-B., Qi, J., Yang, K.-Z., Wu, Y., Wang, K., Wang, C.-B., & Sun, X.-J. (2019) · International Journal of Oncology · doi:10.3892/ijo.2019.4692 · Cited by 109 · see citing works
“The interaction between FXR and NF-κB has been reported in the hepatic inflammatory response (30).”
BackgroundBile Acids and Cancer: Direct and Environmental-Dependent Effects
Ciaula, A. D., Wang, D. Q. ‐., Molina‐Molina, E., Baccetto, R., Calamita, G., Palmieri, V. O., & Portincasa, P. (2017) · Annals of Hepatology · doi:10.5604/01.3001.0010.5501 · Cited by 115 · see citing works
Tissue-specific actions of FXR in metabolism and cancer
Gadaleta, R. M., Cariello, M., Sabbà, C., & Moschetta, A. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.08.005 · Cited by 110 · see citing works
Role of TGR5 (GPBAR1) in Liver Disease
Häussinger, D., & Keitel, V. (2018) · Seminars in Liver Disease · doi:10.1055/s-0038-1669940 · Cited by 106 · see citing works
The Role and Mechanism of Oxidative Stress and Nuclear Receptors in the Development of NAFLD
Hong, T., Chen, Y., Li, X., & Lü, Y. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6889533 · Cited by 104 · see citing works
“Nrf2 negatively controls the NFκB signaling pathway by multiple mechanisms, including inhibiting nuclear translocation of NF-κB and blocking the degradation of IκB-α [89].”
BackgroundAnti-inflammatory and metabolic actions of FXR: Insights into molecular mechanisms
Hollman, D. A. A., Milona, A., van Erpecum, K. J., & van Mil, S. W. C. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.07.004 · Cited by 108 · see citing works
“Recently, FXR activation was observed to decrease the severity of inflammation in the intestine, liver and kidney in vivo [54,55,94,95].”
BackgroundMethodInfluentialPassos, F. R. S., Araújo-Filho, H. G., Monteiro, B. S., Shanmugam, S., Araújo, A. A. D. S., Almeida, J. R. G. D. S., Thangaraj, P., Quintans‐Júnior, L. J., & Quintans, J. D. S. S. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153842 · Cited by 110 · see citing works
The gut microbiome-bile acid axis in hepatocarcinogenesis
Wu, L., Feng, J., Li, J., Yu, Q., Ji, J., Wu, J., Dai, W., & Guo, C. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.111036 · Cited by 103 · see citing works
Nuclear Receptors as Drug Targets in Cholestatic Liver Diseases
Halilbasic, E., Baghdasaryan, A., & Trauner, M. A. (2013) · Clinics in Liver Disease · doi:10.1016/j.cld.2012.12.001 · Cited by 98 · see citing works
“that FXR-deficient mice showed increased baseline hepatic inflammation and are more prone to LPS-induced liver injury(67,83) suggests a direct anti-inflammatory role of FXR, which has been be explained via direct interference with the nuclear factor kappa-B (NF-kB).(83) Notably, this effect is not only hepatocyte-spec…”
Background
- Authors
- Wang, Y.-D., Chen, W.-D., Wang, M., Yu, D., Forman, B. M., & Huang, W.
- Affiliations
- City Of Hope National Medical Center (US)
- Corresponding author
- Huang, Wendong
- Venue
- Hepatology
- Published
- 2008-11
- Volume
- 48
- Issue
- 5
- Pages
- 1632-1643
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC3056574
- OpenAlex
- W2021998283
- Cited by
- 639
- References
- 52
- Citations by year
- 2026: 30 · 2025: 46 · 2024: 44 · 2023: 46 · 2022: 51 · 2021: 54 · 2020: 45 · 2019: 42 · 2018: 31 · 2017: 42 · 2016: 38 · 2015: 29 · 2014: 31 · 2013: 27 · 2012: 27
- FWCI
- 9.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Sidney Kimmel Foundation for Cancer Research
- Sidney Kimmel Foundation
- National Cancer Institute (P30CA033572)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- farnesoid X receptor, nuclear factor-kappaB, liver inflammation, hepatoprotection, lipopolysaccharide, inducible nitric oxide synthase, cyclooxygenase-2, CXCL10, interferon-gamma, liver necrosis, hepatocarcinogenesis, anti-apoptotic genes
- MeSH terms
- Receptor, Farnesoid X-Activated, Animals, Cell Line, DNA-Binding Proteins, Homeostasis, Humans, Inflammation, Kidney, Liver, Liver Neoplasms, Necrosis, RNA, Messenger, Transcription Factors, Tumor Necrosis Factor-alpha, NF-kappa B, Receptors, Cytoplasmic and Nuclear, Hepatoblastoma, Mice, Knockout, Cell Line, Tumor, Mice, Cyclooxygenase 2, Nitric Oxide Synthase Type II
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