The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
FXR Inhibits Endoplasmic Reticulum Stress-Induced NLRP3 Inflammasome in Hepatocytes and Ameliorates Liver Injury
Open accessAbstract
Endoplasmic reticulum (ER) stress is associated with liver injury and fibrosis, and yet the hepatic factors that regulate ER stress-mediated inflammasome activation remain unknown. Here, we report that farnesoid X receptor (FXR) activation inhibits ER stress-induced NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in hepatocytes. In patients with hepatitis B virus (HBV)-associated hepatic failure or non-alcoholic fatty liver disease, and in mice with liver injury, FXR levels in the liver inversely correlated with the extent of NLRP3 inflammasome activation. Fxr deficiency in mice augmented the ability of ER stress to induce NLRP3 and thioredoxin-interacting protein (TXNIP), whereas FXR ligand activation prevented it, ameliorating liver injury. FXR attenuates CCAAT-enhancer-binding protein homologous protein (CHOP)-dependent NLRP3 overexpression by inhibiting ER stress-mediated protein kinase RNA-like endoplasmic reticulum kinase (PERK) activation. Our findings implicate miR-186 and its target, non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1), in mediating the inhibition of ER stress by FXR. This study provides the insights on how FXR regulation of ER stress ameliorates hepatocyte death and liver injury and on the molecular basis of NLRP3 inflammasome activation.
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Cites
Thioredoxin-interacting protein links oxidative stress to inflammasome activation
Zhou, R., Tardivel, A., Thorens, B., Choi, I., & Tschopp, J. (2010) · Nature Immunology · doi:10.1038/ni.1831 · Cited by 2,708
The thioredoxin antioxidant system
Lu, J., & Holmgren, A. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.07.036 · Cited by 2,055
UPR, autophagy, and mitochondria crosstalk underlies the ER stress response
Senft, D., & Ronai, Z. A. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.01.002 · Cited by 1,121
Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR
Calkin, A. C., & Tontonoz, P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3312 · Cited by 779
New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond
Beuers, U., Trauner, M., Jansen, P., & Poupon, R. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.023 · Cited by 537
Mitochondria: diversity in the regulation of the NLRP3 inflammasome
Gurung, P., Lukens, J. R., & Kanneganti, T.-D. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.11.008 · Cited by 393
FXR: a metabolic regulator and cell protector
Wang, Y.-D., Chen, W.-D., Moore, D. D., & Huang, W. (2008) · Cell Research · doi:10.1038/cr.2008.289 · Cited by 389
Farnesoid 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
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Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002
Targeting fibrosis: mechanisms and clinical trials
Zhao, M., Wang, L., Wang, M., Zhou, S., Lu, Y., Cui, H., Racanelli, A. C., Zhang, L., Ye, T., Ding, B., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01070-3 · Cited by 547
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
Wang, Q., Ou, Y., Hu, G., Wen, C., Yue, S., Chen, C., Xu, L., Xie, J., Dai, H., Xiao, H., et al. (2020) · British Journal of Pharmacology · doi:10.1111/bph.14938 · Cited by 309
Endoplasmic reticulum stress-mediated cell death in liver injury
Zhang, J., Guo, J., Yang, N., Huang, Y., Hu, T., & Rao, C. (2022) · Cell Death & Disease · doi:10.1038/s41419-022-05444-x · Cited by 281
Metadata
- Authors
- Han, C. Y., Rho, H. S., Kim, A., Kim, T. H., Jang, K., Jun, D. W., Kim, J. W., Kim, B., & Kim, S. G.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 24
- Issue
- 11
- Pages
- 2985-2999
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2890657719
- Cited by
- 232
- References
- 8
- FWCI
- 7.49
- Type
- journal article
- Language
- en
- Open access
- gold
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