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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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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]
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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
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
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Items 301–400 of 577
Novel treatment options for portal hypertension
Schwabl, P., & Laleman, W. (2017) · Gastroenterology report · doi:10.1093/gastro/gox011 · Cited by 31
van Schaik, F. D. M., Gadaleta, R. M., Schaap, F. G., van Mil, S. W. C., Siersema, P. D., Oldenburg, B., & van Erpecum, K. J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049706 · Cited by 25
“It has been shown that FXR activation can inhibit NF-kB in the intestine as well as in other organs [10,12,19] Phase 3 clinical trials are currently being performed to investigate the potential beneficial effects of a semisynthetic FXR ligand (6-ethyl-chenodeoxycholic acid) in chronic cholestatic liver diseases such a…”
BackgroundGene expression profiles of human liver cells mediated by hepatitis B virus X protein
Zhang, W.-Y., Xu, F.-Q., Shan, C., Xiang, R., Ye, L.-H., & Zhang, X.-D. (2009) · Acta Pharmacologica Sinica · doi:10.1038/aps.2009.22 · Cited by 27
Zhang, M., Xiao, B., Chen, X., Ou, B., & Wang, S. (2023) · Acta Physiologica · doi:10.1111/apha.14065 · Cited by 28
Cao, L., Qin, R., & Liu, J.-B. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110080 · Cited by 26
Nuclear receptors: a bridge linking the gut microbiome and the host
Wang, Z., Chen, W., & Wang, Y. (2021) · Molecular Medicine · doi:10.1186/s10020-021-00407-y · Cited by 29
Self-citationWang, M., Liu, F., Yao, Y., Zhang, Q., Lu, Z., Zhang, R., Liu, C., Lin, C., & Zhu, C. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.113816 · Cited by 29
Self-citationImpaired Gut–Systemic Signaling Drives Total Parenteral Nutrition-Associated Injury
Guzman, M. A., Manithody, C., Krebs, J., Denton, C., Besmer, S., Rajalakshmi, P., Jain, S., Villalona, G. A., & Jain, A. (2020) · Nutrients · doi:10.3390/nu12051493 · Cited by 26
“021), which is known to regulate both intrahepatic bile acid metabolism and hepatic inflammation [41,42], as well as the key hepatic endobiotic detoxifier, the constitutive androstane receptor (CAR) [43,44], a known member of the nuclear receptor superfa ily (p = 0.”
BackgroundFXR Deletion in Hepatocytes does not Affect the Severity of Alcoholic Liver Disease in Mice
Zhang, M., Kong, B., Huang, M.-X., Wan, R.-X., Armstrong, L. E., Schumacher, J. D., Rizzolo, D., Chow, M. D., Lee, Y.-H., & Guo, G. L. (2018) · Digestive and Liver Disease · doi:10.1016/j.dld.2018.04.009 · Cited by 26
Kong, Y., Gao, X., Wang, C.-Y., Ning, C., Liu, K.-X., Liu, Z.-H., Sun, H.-J., Ma, X., Sun, P., & Meng, Q. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.02.002 · Cited by 26
“Recent report has demonstrated that FXR plays a novel role in the control of liver inflammation through inhibiting NF-κB signaling pathway (Wang et al., 2008).”
BackgroundDeletion of IFNγ enhances hepatocarcinogenesis in FXR knockout mice
Meng, Z.-P., Wang, X.-Q., Gan, Y., Zhang, Y., Zhou, H., van Ness, C., Wu, J., Lou, G., Yu, H., He, C., et al. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.06.016 · Cited by 26
Self-citationGao, Y., Lin, J., Ye, C., Guo, S., & Jiang, C. (2023) · Liver Research · doi:10.1016/j.livres.2023.09.002 · Cited by 26
Zhao, Y., Wei, S., Chen, L., Zhou, X., & Ma, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1164202 · Cited by 38
Chen, X., Chen, Y., Stanton, C., Ross, R., Zhao, J.-X., Chen, W., & Yang, B. (2023) · Nutrients · doi:10.3390/nu15081952 · Cited by 25
“It has been reported that FXR activation inhibits NF-κB nuclear translocation in various diseases [37,38].”
BackgroundSelf-citationXiao, F., Gao, X., Hu, H., Le, J., Chen, Y., Shu, X., Liang, Z., Xu, Y., Wang, Y., & Zhang, T. (2022) · Nutrients · doi:10.3390/nu14214463 · Cited by 25
Self-citationPallozzi, M., Tommaso, N. D., Maccauro, V., Santopaolo, F., Gasbarrini, A., Ponziani, F. R., & Pompili, M. (2022) · Cancers · doi:10.3390/cancers14194631 · Cited by 27
McIlvride, S., Nikolova, V., Fan, H. M., McDonald, J. A. K., Wahlstrom, A. M., Bellafante, E., Jansen, E. H. J. M., Adorini, L., Shapiro, D., Jones, P. M., et al. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00407.2018 · Cited by 26
“FXR has been shown to regulate inflammatory responses via nuclear factor B (59), and OCA has previously been shown to reduce expression of inflammatory markers in adipose tissue (22).”
BackgroundFXR Agonists: From Bench to Bedside, a Guide for Clinicians
Alawad, A., & Levy, C. (2016) · Digestive Diseases and Sciences · doi:10.1007/s10620-016-4334-8 · Cited by 25
“In addition to reducing the BA pool and changing the bile composition, FXR activation leads to induction of fibroblast growth factor 19 (FGF 19) and anti-inflammatory effects through inhibition of NF-Kb [8, 9].”
Yamada, T., Osawa, S., Ikuma, M., Kajimura, M., Sugimoto, M., Furuta, T., Iwaizumi, M., & Sugimoto, K. (2014) · Digestion · doi:10.1159/000365750 · Cited by 25
Yang, J.-Y., Liu, M., Lv, L. L., Guo, J.-R., He, K.-Y., Zhang, H., Wang, K., Cui, C.-Y., Yan, B., Du, D., et al. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.932294 · Cited by 21
“Lack of FXR is associated with increased intestinal permeability of the gastrointestinal tract (Wang et al., 2008; Gadaleta et al., 2011).”
BackgroundStrathearn, L. S., Stepanov, A. I., & Font-Burgada, J. (2020) · Nutrients · doi:10.3390/nu12040933 · Cited by 26
Fuchs, C. D., Krivanec, S., Steinacher, D., Mlitz, V., Wahlstrom, A. M., Ståhlman, M., Claudel, T., Scharnagl, H., Stojaković, T., Marschall, H., et al. (2020) · Liver International · doi:10.1111/liv.14423 · Cited by 26
Identification of FDA-approved drugs targeting the Farnesoid X Receptor
van de Wiel, S. M. W., Bijsmans, I. T. G. W., van Mil, S. V., & van de Graaf, S. V. D. (2019) · Scientific Reports · doi:10.1038/s41598-019-38668-7 · Cited by 24
Clinical Trial Design for Alcoholic Hepatitis
Szabó, G. (2017) · Seminars in Liver Disease · doi:10.1055/s-0037-1608788 · Cited by 24
Non-Alcoholic Steatohepatitis: From Pathophysiology to Novel Therapies
Jahn, D., Rau, M., Wohlfahrt, J., Hermanns, H. M., & Geier, A. (2016) · Digestive Diseases · doi:10.1159/000444547 · Cited by 32
Koutsounas, I. S., Theocharis, S. E., Delladetsima, I. K., Patsouris, E., & Giaginis, C. (2015) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2014.999664 · Cited by 25
“FXR agonists may also target inflammation and fibrosis, helping to counteract the consequences of cholestatic liver injury, probably by interfering with NFkB signaling [51].”
BackgroundBile Acids and Biliary Fibrosis
Aseem, S. O., Hylemon, P. B., & Zhou, H. (2023) · Cells · doi:10.3390/cells12050792 · Cited by 28
“FXR has immune-modulating effects through interactions with NF-κB in hepatocytes and various immune cells, leading to the suppression of NF-κBinduced inflammatory cytokines [7,63,64].”
BackgroundAn, J., & Sohn, J. H. (2022) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2022.0437 · Cited by 24
“The farnesoid X receptor activation can help reduce hepatic inflammation and fibrosis.(29,30) Obeticholic acid is a potent and selective farnesoid X receptor agonist.”
BackgroundJung, H.-K., Chen, J., Hu, X., Sun, H., Wu, S.-Y., Chiang, C., KEMPER, B. W., Chen, L., & Kemper, J. K. (2020) · JCI Insight · doi:10.1172/jci.insight.141640 · Cited by 30
Roles of the inflammasome in the gut‑liver axis (Review)
Wang, J., Dong, R., & Zheng, S. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9679 · Cited by 31
Role of Bile Acid Receptors in the Development and Function of Diabetic Nephropathy
Fang, Y., Qin, M., Zheng, Q., Wang, K., Han, X., Yang, Q., Sang, X., & Cao, G. (2024) · Kidney International Reports · doi:10.1016/j.ekir.2024.08.002 · Cited by 21
What role for cellular metabolism in the control of hepatitis viruses?
Diaz, O., Vidalain, P., Ramière, C., Lotteau, V., & Perrin‐Cocon, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1033314 · Cited by 22
Liu, C., Pan, Z., Wu, Z.-L., Tang, K., Zhong, Y., Chen, Y., Xiao, X., Guo, J., Duan, S., Cui, T., et al. (2022) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2022.04.011 · Cited by 25
“Moreover, the direct interaction between FXR and NF-kB confers critical anti-inflammatory features of FXR in hepatoprotection.(49,50) Based on the fact that SIRT6 together”
BackgroundFrancis, M., Guo, G. L., Kong, B., Абрамова, Е. В., Cervelli, J. A., Gow, A. J., Laskin, J. D., & Laskin, D. L. (2020) · Toxicological Sciences · doi:10.1093/toxsci/kfaa111 · Cited by 31
“…with an exacerbated inflammatory response, characterized by increases in infiltrating macrophages and upregulation proinflammatory genes in experimental models of lung, liver, and intestinal disease pathology (Shaik et al., 2015; Vavassori et al., 2009; Wang et al., 2008; Zhang et al., 2012).”
BackgroundInfluentialmiRNA-149* suppresses liver cancer progression by down-regulating TRADD protein expression.
Feng, Q., Zhang, H.-L., Nie, X.-B., Li, Y., Chen, W.-D., & Wang, Y.-D. (2019) · American Journal of Pathology · doi:10.1016/j.ajpath.2019.10.010 · Cited by 22
Self-citationTakahashi, S., Tanaka, N., Golla, S., Fukami, T., Krausz, K. W., Polunas, M., Weig, B., Masuo, Y., Xie, C., Jiang, C., et al. (2017) · Toxicological Sciences · doi:10.1093/toxsci/kfx094 · Cited by 24
“It was documented that Fxr / mice exhibited more severe inflammation under several diseased conditions, and the mechanism was explained as counteracting the effect of FXR against NF-jB signaling in Kupffer cells (Wang et al., 2008).”
BackgroundBile salt signaling and bile salt-based therapies in cardiometabolic disease
Groenen, C., Nguyen, T.-A., Paulusma, C. C., & van de Graaf, S. F. J. (2024) · Clinical Science · doi:10.1042/cs20230934 · Cited by 25
Cui, H., Han, S., Dai, Y., Xie, W., Zheng, R., Sun, Y., Xia, X., Deng, X., Cao, Y., Zhang, M., et al. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.154885 · Cited by 23
Obeticholic Acid Induces Hepatoxicity Via FXR in the NAFLD Mice
Lin, C., Yu, B., Chen, L., Zhang, Z., Ye, W., Zhong, H., Bai, W., Yang, Y., & Nie, B. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.880508 · Cited by 17
Wang, Y., Nan, X., Zhao, Y., Jiang, L., Wang, H., Zhang, F., Hua, D., Liu, J., Yang, L., Yao, J., et al. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.809139 · Cited by 27
Self-citationBile-ology: from bench to bedside
Jin, L., Fang, Z., Fan, M.-J., & Huang, W. (2019) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b1900158 · Cited by 22
Self-citationTsuchiya, T., Naitoh, T., Nagao, M., Tanaka, N., Watanabe, K., Imoto, H., Miyachi, T., Motoi, F., & Unno, M. (2017) · Obesity Surgery · doi:10.1007/s11695-017-3065-z · Cited by 21
“The FXR and its target transcriptional factor, small heterodimer partner (SHP), inhibit the nuclear factor-κB (NF-κB) signaling and decrease pro-inflammatory cytokine production in the liver [33].”
BackgroundLiu, H.-M., Lee, T.-Y., & Liao, J. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.3366 · Cited by 24
“FXR inhibits the inflammatory response through several mechanisms, including the formation of direct complexes with NF‑ κ B family members and/or the modulation of MAPK activity (9,24).”
InfluentialHe, X., Shi, J., Bu, L., Zhou, S., Wu, K., Liang, G., Xu, X., & Wang, A.-Z. (2024) · Biochemical Pharmacology · doi:10.1016/j.bcp.2024.116574 · Cited by 20
Li, Y., Chen, L., Sottas, C. M., Raul, M. C., Patel, N. D., Bijja, J. R., Ahmed, S. K., Kapelanski‐Lamoureux, A., Lazaris, A., Metrakos, P. P., et al. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155942 · Cited by 18
Fuchs, C. D., SRODA, N., Scharnagl, H., Gupta, R. S., Minto, W. C., Stojaković, T., Liles, J. T., Budas, G. R., Hollenback, D., & Trauner, M. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100874 · Cited by 22
Gehrke, N., Hofmann, L. J., Straub, B. K., Rühle, F., Waisman, A., Galle, P. R., & Schattenberg, J. M. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.1048 · Cited by 23
Orabi, D., Berger, N. A., & Brown, J. M. (2021) · Cancers · doi:10.3390/cancers13143473 · Cited by 25
“FXR knockout mice show increased levels of hepatic inflammation, notably through NF-κB activation [168], and display higher rates of HCC development [169–171].”
BackgroundA Novel Class of Natural FXR Modulators with a Unique Mode of Selective Co‐regulator Assembly
Zheng, W., Lu, Y. P., Lin, S., Wang, R. Y., Qiu, L., Zhu, Y., Yao, B., Guo, F., Jin, S., Jin, L., et al. (2017) · ChemBioChem · doi:10.1002/cbic.201700059 · Cited by 26
Farnesoid X receptor as a regulator of fuel consumption and mitochondrial function
Han, C. Y., Kim, T. H., Koo, J. H., & Kim, S. G. (2016) · Archives of Pharmacal Research · doi:10.1007/s12272-016-0812-y · Cited by 23
Farnesoid X Receptor (FXR) from normal to malignant state.
Koutsounas, I., Giaginis, C., & Theocharis, S. (2012) · Histology and Histopathology · doi:10.14670/hh-27.835 · Cited by 20
“Additionally, several synthetic FXR ligands have been generated, such as GW4064, 6ECDCA, AGN29, and AGN31, with GW4064 being the most widely used (Wang et al., 2008a) (Fig.”
BackgroundMethodInfluentialPotential of Intestine-Selective FXR Modulation for Treatment of Metabolic Disease
van Zutphen, T., Bertolini, A., de Vries, H. D., Bloks, V. W., de Boer, J. F., Jonker, J. W., & Kuipers, F. (2019) · Handbook of experimental pharmacology · doi:10.1007/164_2019_233 · Cited by 31
Deficiency of miRNA-149-3p shaped gut microbiota and enhanced dextran sulfate sodium-induced colitis
Feng, Q., Li, Y., Zhang, H., Wang, Z., Nie, X., Yao, D., Lu, H., Chen, W., & Wang, Y. (2022) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2022.09.018 · Cited by 19
“Proteins were isolated from cells or mouse colons, and then SDSPAGE was performed to separate proteins as described previously.(21,47) Bands on blots were visualized, and protein expression was analyzed with a computerized digital imaging system using Tanon software.”
MethodSelf-citationFXR/TGR5 mediates inflammasome activation and host resistance to bacterial infection
Kang, J., Kim, M., & Yim, M. (2021) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2021.101051 · Cited by 16
Ni, Q., Cai, C., Ren, S., Zhang, J., Zhao, Y., Wei, X., Ge, Y., Wang, C., Li, W., Wu, P., et al. (2021) · Aquaculture Research · doi:10.1111/are.15140 · Cited by 21
Darvin, S. S., Toppo, E., Esakkimuthu, S., Krishna, T. P. A., Ceasar, S. A., Stalin, A., Balakrishna, K., Muniappan, N., Pazhanivel, N., Mahaprabhu, R., et al. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.09.116 · Cited by 23
Li, Y., Wu, J., Dai, Y., Dai, Y., Zheng, M., Zeng, J., Wang, G.-F., Wang, T., Li, W.-K., Zhang, X.-Y., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.21385 · Cited by 19
“FXR activation can also inhibit NF-κΒ pathway-mediated inflammation [44, 45].”
BackgroundBaicalein induces the apoptosis of U251 glioblastoma cell lines via the NF-kB-p65-mediated mechanism
Jiang, G., Zhang, L., Wang, J.-K., & Zhou, H.-J. (2016) · doi:10.1080/19768354.2016.1229216 · Cited by 19
“Dysregulation of the NF-kB pathway has been linked to many diseases, including inflammatory and autoimmune diseases, viral infection, cancers, etc. (Raza et al. 2007; Wang et al. 2008).”
BackgroundIntestinal failure to produce FGF19: A culprit in intestinal failure–associated liver disease?
van Erpecum, K. J., & Schaap, F. G. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.03.012 · Cited by 22
“Apart from preventing derangement of bile salt homeostasis, restored intestinal barrier function and anti-inflammatory effects through inhibition of NF-jB are likely to be involved in these beneficial effects [4,13].”
BackgroundA novel heterozygous NR1H4 termination codon mutation in idiopathic infantile cholestasis
Chen, X.-Q., Wang, L.-L., Shan, Q., Tang, Q., Deng, Y.-N., Lian, S.-J., & Yun, X. (2012) · World Journal of Pediatrics · doi:10.1007/s12519-011-0299-z · Cited by 19
Farnesoid X Receptor Agonists: What They Are and How They Might Be Used in Treating Liver Disease
Neuschwander‐Tetri, B. A. (2011) · Current Gastroenterology Reports · doi:10.1007/s11894-011-0232-6 · Cited by 18
Fousekis, F. S., Mpakogiannis, K. C., Lianos, G. D., Antonelli, E., Bassotti, G., & Katsanos, K. H. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14217817 · Cited by 19
Zhao, W.-W., Xiao, M., Wu, X., Li, X., Li, X.-X., Zhao, T., Yu, L., & Chen, X.-Q. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.771976 · Cited by 18
“The mRNA expression levels of TNF-α and IL-6, two inflammatory genes regulated by NF-κB, were significantly increased in the HFD group, which were reduced in the IsA group (Figures 2G, H).”
BackgroundInfluentialGuo, J., Akahoshi, T., Mizuta, Y., Murata, M., Narahara, S., Kawano, T., Nagao, Y., Zhang, S., Tomikawa, M., Kawanaka, H., et al. (2020) · Liver transplantation · doi:10.1002/lt.25960 · Cited by 18
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Trivella, J. P., Martin, P. B., & Carrion, A. F. (2020) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2020.1735350 · Cited by 19
“FXR expression has also been demonstrated in quiescent and activated HSCs and ligand activation has been associated with anti-inflammatory effects through inhibition of NF-kB [57,58] and decreased collagen synthesis [59].”
BackgroundProteome Profiling in Lung Injury Following Hematopoietic Stem Cell Transplantation
Bhargava, M., Viken, K., Dey, S., Steinbach, M. S., Wu, B.-L., Jagtap, P., Higgins, L., Panoskaltsis-Mortari, A., Weisdorf, D., Kumar, V., et al. (2016) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2016.04.021 · Cited by 18
Nijmeijer, R. M., Schaap, F. G., Smits, A. J. J., Kremer, A. E., Akkermans, L. M. A., Kroese, A. B. A., Rijkers, G. T., Schipper, M. E. I., Verheem, A., Wijmenga, C., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114393 · Cited by 17
“The underlying mechanism for these anti-inflammatory effects is thought to be inhibition of NF-kB [16].”
Jiao, Y., Ren, J., Xie, S., Yuan, N., Shen, J., Yin, H., Wang, J., Guo, H., Cao, J., Wang, X., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2488105 · Cited by 16
“FXR activation triggered downstream pathways, 21,42 particularly the inhibition of NF-κB signaling, 22,23,43–45 which was known to regulate inflammatory and immune responses.”
Gut Microbiome and Bile Acid Interactions
Wu, N., Bayatpour, S., Hylemon, P. B., Aseem, S. O., Brindley, P. J., & Zhou, H. (2024) · American Journal Of Pathology · doi:10.1016/j.ajpath.2024.11.004 · Cited by 15
Sheng, X., Zhan, P., Wang, P., He, W., & Tian, H. (2024) · Food & Function · doi:10.1039/d3fo05235d · Cited by 20
Prasoppokakorn, T., Pitisuttithum, P., & Treeprasertsuk, S. (2021) · Journal of Clinical and Translational Hepatology · doi:10.14218/jcth.2021.00189 · Cited by 24
The role of the gut microbiome in graft fibrosis after pediatric liver transplantation
Qin, T., Fu, J., & Verkade, H. J. (2020) · Human Genetics · doi:10.1007/s00439-020-02221-8 · Cited by 18
Zhu, Y., Xu, S., Lu, Y., Wei, Y., Yao, B., Guo, F., Zheng, X., Wang, Y., He, Y., Jin, L.-H., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00590 · Cited by 17
“On the other hand, activation of FXR suppressed the induction of inflammation genes in the liver and intestine, possibly by repression of NF-kB signaling (Wang et al., 2008; Vavassori et al., 2009; Gadaleta et al., 2011a; Gadaleta et al., 2011b).”
BackgroundSelf-citationYang, R., Hu, Z., Zhang, P., Wu, S., Song, Z., Shen, X., & Wei, Z. (2018) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2018.12.005 · Cited by 18
Wigger, L., Casals‐Casas, C., Baruchet, M., Trang, B. K., Pradervand, S., Naldi, A., & Desvergne, B. (2019) · PLoS ONE · doi:10.1371/journal.pone.0220894 · Cited by 19
Altered zinc balance in the Atp7b−/− mouse reveals a mechanism of copper toxicity in Wilson disease
Meacham, K. A., Cortés, M. P., Wiggins, E. M., Maass, A., Latorre, M., Ralle, M., & Burkhead, J. L. (2018) · Metallomics · doi:10.1039/c8mt00199e · Cited by 22
Dietary and metabolic modulators of hepatic immunity
Carambia, A., & Herkel, J. (2017) · Seminars in Immunopathology · doi:10.1007/s00281-017-0659-4 · Cited by 17
Honke, N., Shaabani, N., Hardt, C., Krings, C., Häussinger, D., Lang, P. A., Lang, K. S., & Keitel, V. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000456168 · Cited by 18
Bile acids and liver carcinogenesis: TGR5 as a novel piece in the puzzle?
Péan, N., Doignon, I., & Tordjmann, T. (2013) · Clinics And Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2012.12.005 · Cited by 17
Jansen, P. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.02.003 · Cited by 17
Chen, C., Zhang, B., Tu, J., Peng, Y., Zhou, Y., Yang, X., Yu, Q.-M., & Tan, X. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115992 · Cited by 16
Farnesoid X receptor: a potential therapeutic target in multiple organs.
Zhang, C., Wang, Z., Feng, Q., Chen, W.-D., & Wang, Y.-D. (2021) · Histology and Histopathology · doi:10.14670/hh-18-301 · Cited by 16
“The expression of various isoforms of FXR is somewhat different in mice (Wang et al., 2008a; Vaquero et al., 2013a).”
InfluentialSelf-citationMasaoutis, C., & Theocharis, S. (2018) · Expert opinion on therapeutic targets · doi:10.1080/14728222.2019.1559825 · Cited by 16
“More precisely, pretreatment of mice with FXR agonist obeticholic acid brought about multiple anti-inflammatory and antioxidant effects in a time-dependent manner: it suppressed the renal production of inflammatory factors TNF-α, IL-6, IL-1β, CXCL2, CXCL1 and CCL2 (but not COX2 or TGF-β), blocked the nuclear transloca…”
BackgroundInfluentialFrom pathogenesis to novel therapies in the treatment of primary biliary cholangitis
Ronca, V., Carbone, M., Bernuzzi, F., Malinverno, F., Mousa, H. S., Gershwin, M. E., & Invernizzi, P. (2017) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2017.1391093 · Cited by 18
Cheng, Q., Inaba, Y., Lu, P., Xu, M., He, J., Zhao, Y., Guo, G. L., Kuruba, R., de la Vega, R., Evans, R. G., et al. (2015) · Molecular Endocrinology · doi:10.1210/me.2014-1337 · Cited by 22
Evolving therapies for non-alcoholic steatohepatitis
Tilg, H., & Moschen, A. R. (2014) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2014.911283 · Cited by 18
“It beneficially controls liver inflammation in an NF-kB-dependent manner [74], and affects glucose/lipid metabolism and fibrosis in various preclinical models [75].”
BackgroundJang, E. S., Yoon, J., Lee, S., Lee, S.-M., Lee, J., Yu, S. J., Kim, Y. J., Lee, H., & Kim, C. Y. (2013) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-013-1554-6 · Cited by 18
“Because FXR antagonizes NFκB in HepG2 cells and primary hepatocytes (Wang et al. 2008), the reversal of IL-8 overexpression in Huh-7 cells after guggulsterone treatment might not be mediated by FXR.”
BackgroundAzizsoltani, A., Niknam, B., Taghizadeh-Teymorloei, M., Ghoodjani, E., Dianat-Moghadam, H., & Alizadeh, E. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118249 · Cited by 15
Wang, X., Klaassen, C. D., Chen, X., & Zhang, Y. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100073 · Cited by 17
Gu, M., Feng, Y., Chen, Y., Fan, S., & Huang, C. (2023) · Phytotherapy Research · doi:10.1002/ptr.7770 · Cited by 15
“Additionally, both FXR and TGR5 activation antagonize NF-κB (Jiao et al., 2022; Wang et al., 2008).”
BackgroundMechanism of KLF4 Protection against Acute Liver Injury via Inhibition of Apelin Signaling
Ji, W., Shi, H., Shen, H., Kong, J., Song, J.-Y., Bian, H.-Y., & Lv, X.-R. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/6140360 · Cited by 15
“Acute liver injury can arise from multiple factors, including viral infection, trauma, or chemical reagents, such as alcohol, drugs, and toxic substance [1, 2].”
BackgroundXie, S., Guo, C., Chi, Z., Huang, B., Wu, Y., Wang, D., & Xia, D. (2017) · FEBS Letters · doi:10.1002/1873-3468.12782 · Cited by 15
Wang, J., Zhang, Y., Wu, Q., Zhong, Y., Xu, Z., & Yang, J. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1757551 · Cited by 10
Immune Checkpoints and the Immunology of Liver Fibrosis
Tsomidis, I., Voumvouraki, A., & Kouroumalis, E. (2025) · Livers · doi:10.3390/livers5010005 · Cited by 14
Alruhaimi, R. S., Alotaibi, M. F., Alnasser, S., Alzoghaibi, M., Germoush, M., Alotaibi, M., Hassanein, E. H. M., & Mahmoud, A. M. (2024) · Food and Chemical Toxicology · doi:10.1016/j.fct.2024.114788 · Cited by 14
Vu, V., Kim, Y. M., & Cho, M.-J. (2023) · Applied Biological Chemistry · doi:10.1186/s13765-022-00755-1 · Cited by 14
Isotschimgine alleviates nonalcoholic steatohepatitis and fibrosis via FXR agonism in mice
Li, J., Liu, C., Zhou, Z., Dou, B., Huang, J.-W., Huang, L., Zheng, P.-Y., Fan, S., & Huang, C. (2021) · Phytotherapy Research · doi:10.1002/ptr.7055 · Cited by 14
Shah, R. A., Alkhouri, N., & Kowdley, K. V. (2020) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2020.1796968 · Cited by 15
Gu, M., Song, H.-Y., Li, Y., Jiang, Y.-W., Zhang, Y.-L., Tang, Z., Ji, G., & Huang, C. (2020) · Phytotherapy Research · doi:10.1002/ptr.6743 · Cited by 14
Reversal of NASH fibrosis with pharmacotherapy
Alukal, J. J., & Thuluvath, P. J. (2019) · Hepatology International · doi:10.1007/s12072-019-09970-3 · Cited by 17
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
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