The DOI matches its Crossref record; 49 of the 52 references it cites were found in a registry or an index.
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.)
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“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]
Experimental — accuracy not yet measuredIn the citing paper
“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
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
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
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 3,175
Wang, C.-Y., Mayo, M., Korneluk, R., Goeddel, D., & Baldwin, A. (1998) · Science · doi:10.1126/science.281.5383.1680 · Cited by 2,950
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
NF-κB functions as a tumour promoter in inflammation-associated cancer
Pikarsky, E., Porat, R. M., 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 2,423
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
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
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
Self-citationAggarwal, B. B. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.09.003 · Cited by 1,586
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 1,287
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
Chait, A., & den Hartigh, L. J. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00022 · Cited by 1,529
Bile Acid Metabolism and Signaling
Chiang, J. Y. L. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120023 · Cited by 1,662
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
“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
Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives
Roehlen, N., Crouchet, E., & Baumert, T. F. (2020) · Cells · doi:10.3390/cells9040875 · Cited by 1,237
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
“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
Postler, T. S., & Ghosh, S. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.05.008 · Cited by 876
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
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
“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
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 641
“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 615
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
“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
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
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 424
Bile Acid Metabolism in Liver Pathobiology
Chiang, J. Y. L., & Ferrell, J. M. (2018) · Gene Expression · doi:10.3727/105221618x15156018385515 · Cited by 571
Wang, Y., Chen, W., Yu, D. D., FORMAN, B. M., & Huang, W. (2011) · Hepatology · doi:10.1002/hep.24525 · Cited by 496
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
“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
“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
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
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 336
“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 262
“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 305
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 283
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 268
“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
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
“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
Self-citationBishehsari, F. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i20.6055 · Cited by 277
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 306
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
TGR5, Not Only a Metabolic Regulator
Guo, C., Chen, W., & Wang, Y. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00646 · Cited by 242
“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
“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
“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
Poupon, R. Y. (2012) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/s2210-7401(12)70015-3 · Cited by 230
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 236
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
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 265
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
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
“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 203
“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
“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
“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 209
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 193
Wang, 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 191
“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 212
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 214
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
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
“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 200
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
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
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 184
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 172
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
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
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
“…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 170
Role of Gut Dysbiosis in Liver Diseases: What Have We Learned So Far?
Fukui, H. (2019) · Diseases · doi:10.3390/diseases7040058 · Cited by 159
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
Baars, A., Oosting, A., Knol, J., Garssen, J., & Van Bergenhenegouwen, J. (2015) · Microorganisms · doi:10.3390/microorganisms3040641 · Cited by 135
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 150
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
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 125
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
“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
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 140
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 115
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
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
“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
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 139
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
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 116
“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
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 122
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 119
“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 126
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 133
Nuclear bile acid signaling through the farnesoid X receptor
Mazuy, C., Helleboid‐Chapman, A., Staels, B., & Lefèbvre, P. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1805-y · Cited by 113
“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
Claudel, T., Zollner, G., Wagner, M., & Trauner, M. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.12.021 · Cited by 104
The role of bile acids in cholestatic liver injury
Cai, S., & Boyer, J. L. (2021) · Annals of Translational Medicine · doi:10.21037/atm-20-5110 · Cited by 129
“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 110
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
“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 119
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 112
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
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 110
“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 112
“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 114
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
Nuclear Receptors as Drug Targets in Cholestatic Liver Diseases
Halilbasic, E., Baghdasaryan, A., & Trauner, M. (2013) · Clinics in Liver Disease · doi:10.1016/j.cld.2012.12.001 · Cited by 100
“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
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
