Editor's Highlight: Farnesoid X Receptor Protects Against Low-Dose Carbon Tetrachloride-Induced Liver Injury Through the Taurocholate-JNK Pathway

Toxicological Sciences : an Official Journal of the Society of Toxicology
Shogo TakahashiFrank J Gonzalez

Abstract

Hepatotoxicity is of major concern for humans exposed to industrial chemicals and drugs. Disruption of farnesoid X receptor (FXR), a master regulator of bile acid (BA) metabolism, enhanced the sensitivity to liver injury in mice after toxicant exposure, but the precise mechanism remains unclear. In this study, the interconnection between BA metabolism, FXR, and chemically induced hepatotoxicity was investigated using metabolomics, Fxr-null mice (Fxr-/-) and hepatocytes, and recombinant adenoviruses. A single low-dose intraperitoneal injection of carbon tetrachloride (CCl4), an inducer of acute hepatitis in mice, resulted in more severe hepatocyte damage and higher induction of pro-inflammatory mediators, such as chemokine (C-C motif) ligand 2 (Ccl2), in Fxr-/-. Serum metabolomics analysis revealed marked increases in circulating taurocholate (TCA) and tauro-β-muricholate (T-β-MCA) in these mice, and forced expression of bile salt export protein (BSEP) by recombinant adenovirus in Fxr-/- ameliorated CCl4-induced liver damage. Treatment of Fxr-null hepatocytes with TCA, but not T-β-MCA, significantly increased c-Jun-N-terminal kinase (JNK) activation and Ccl2 mRNA levels, and up-regulation of Ccl2 mRNA was attenuated by co-treatm...Continue Reading

References

May 12, 2005·Journal of Hepatology·Tetsuya UeharaDavid A Brenner
Mar 25, 2006·The Journal of Clinical Investigation·Ke MaDavid D Moore
Apr 22, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Harm HoekstraPierre A Clavien
Jul 13, 2006·Gastroenterology·Basuki K GunawanNeil Kaplowitz
Nov 28, 2006·Journal of Hepatology·Elena ZamaraFabio Marra
Oct 31, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yan-Dong WangWendong Huang
Dec 23, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jane A ByrneRichard J Thompson
May 2, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Yue J CuiCurtis D Klaassen
Mar 10, 2010·Molecular Endocrinology·Zhipeng MengWendong Huang
Mar 10, 2011·Nature Reviews. Gastroenterology & Hepatology·Shannan Tujios, Robert J Fontana
Apr 12, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tsutomu MatsubaraFrank J Gonzalez
Feb 1, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Naoki TanakaFrank J Gonzalez
May 23, 2012·Molecular and Cellular Endocrinology·Tsutomu MatsubaraFrank J Gonzalez
May 24, 2012·The Journal of Biological Chemistry·Yuanyuan ZhangJohn D Schuetz
Sep 1, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Junko KatoHiroko Tsutsui
Jan 16, 2013·Pharmaceutical Research·Lauren M AleksunesAngela L Slitt
Jan 31, 2013·Toxicology and Applied Pharmacology·Makoto YamazakiLining Guo
May 25, 2013·Liver International : Official Journal of the International Association for the Study of the Liver·Eugenia UlzurrunRaúl J Andrade
Jun 26, 2014·EMBO Molecular Medicine·Jérémie GautheronTom Luedde
Aug 12, 2014·Current Protocols in Toxicology·J Gerry Kenna
Sep 3, 2014·Biochimica Et Biophysica Acta·Naoki TanakaFrank J Gonzalez
Nov 27, 2014·The EMBO Journal·Dong-Hyun KimJongsook Kim Kemper
Dec 17, 2014·The Journal of Clinical Investigation·Changtao JiangFrank J Gonzalez
Mar 22, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Cynthia R L Webster, M Sawkat Anwer
Apr 10, 2016·Biopharmaceutics & Drug Disposition·Yaofeng ChengYurong Lai
Sep 7, 2016·Journal of Hepatology·Claudia D FuchsMichael Trauner
Sep 18, 2016·Journal of Lipid Research·Shogo TakahashiFrank J Gonzalez

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Citations

Jul 18, 2018·International Journal of Molecular Sciences·Chang Yeob Han
Dec 18, 2018·Hepatology Communications·Shogo TakahashiFrank J Gonzalez
Feb 12, 2021·Nature Reviews. Gastroenterology & Hepatology·Lulu SunFrank J Gonzalez
Mar 12, 2021·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Wan PengFei Li
Mar 5, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Tingting YanFrank J Gonzalez
Feb 26, 2019·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Bo KongGrace L Guo
Apr 26, 2021·Pharmacology & Therapeutics·Nana YanFrank J Gonzalez
Jun 30, 2019·Gene Expression·Benjamin L Woolbright, Hartmut Jaeschke

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