Upregulation of early growth response factor-1 by bile acids requires mitogen-activated protein kinase signaling.

Toxicology and Applied Pharmacology
Katryn AllenBryan L Copple

Abstract

Cholestasis results when excretion of bile acids from the liver is interrupted. Liver injury occurs during cholestasis, and recent studies showed that inflammation is required for injury. Our previous studies demonstrated that early growth response factor-1 (Egr-1) is required for development of inflammation in liver during cholestasis, and that bile acids upregulate Egr-1 in hepatocytes. What remains unclear is the mechanism by which bile acids upregulate Egr-1. Bile acids modulate gene expression in hepatocytes by activating the farnesoid X receptor (FXR) and through activation of mitogen-activated protein kinase (MAPK) signaling. Accordingly, the hypothesis was tested that bile acids upregulate Egr-1 in hepatocytes by FXR and/or MAPK-dependent mechanisms. Deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA) stimulated upregulation of Egr-1 to the same extent in hepatocytes isolated from wild-type mice and FXR knockout mice. Similarly, upregulation of Egr-1 in the livers of bile duct-ligated (BDL) wild-type and FXR knockout mice was not different. Upregulation of Egr-1 in hepatocytes by DCA and CDCA was prevented by the MEK inhibitors U0126 and SL-327. Furthermore, pretreatment of mice with U0126 prevented upregulation of ...Continue Reading

References

Apr 3, 1998·Journal of Clinical Laboratory Analysis·M YamashikiF Ichida
May 21, 1999·Science·M MakishimaB Shan
Feb 5, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yi-Ping RaoPhillip B Hylemon
Jul 29, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jaspreet S GujralHartmut Jaeschke
Oct 18, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Jaspreet S GujralHartmut Jaeschke
Apr 16, 2004·Seminars in Liver Disease·Melissa K Li, James M Crawford
Sep 25, 2008·Journal of Cellular Biochemistry·Sabine I MayerGerald Thiel

❮ Previous
Next ❯

Citations

Jul 25, 2014·Toxicological Sciences : an Official Journal of the Society of Toxicology·Anna K KopecJames P Luyendyk
Mar 25, 2011·The Journal of Pharmacology and Experimental Therapeutics·Andy WolfeUdayan Apte
Oct 11, 2012·World Journal of Gastroenterology : WJG·Benjamin L Woolbright, Hartmut Jaeschke
Nov 19, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Bradley P SullivanJames P Luyendyk
Oct 20, 2015·Expert Opinion on Therapeutic Targets·Benjamin L Woolbright, Hartmut Jaeschke
Dec 8, 2015·Experimental and Therapeutic Medicine·Zein Shaban Ibrahim
Mar 13, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yuxia ZhangLi Wang
Jan 13, 2011·The American Journal of Pathology·Ning ShenChao-Jun Li
May 9, 2012·Cellular Signalling·Zhizhen XuFengtian He
Sep 10, 2013·The American Journal of Pathology·Kate M O'BrienBryan L Copple
Jan 12, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dong FuIrwin M Arias
Jun 14, 2017·Molecular Aspects of Medicine·Man LiJames L Boyer
May 7, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Lina SunUdayan Apte
Oct 5, 2013·American Journal of Physiology. Gastrointestinal and Liver Physiology·Guodong LiGrace L Guo
Aug 9, 2020·Frontiers in Pharmacology·Shizhang WeiYanling Zhao
Apr 12, 2019·Archives of Toxicology·Eva GijbelsMathieu Vinken
Jun 20, 2020·European Journal of Pharmacology·Naihua HuYunxia Li
Sep 29, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Mengzhi ZouXinzhi Wang
Jun 30, 2019·Gene Expression·Benjamin L Woolbright, Hartmut Jaeschke

❮ Previous
Next ❯

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

Adrenocortical Carcinoma

Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.

Related Papers

Toxicological Sciences : an Official Journal of the Society of Toxicology
Nam Deuk KimBryan L Copple
Liver International : Official Journal of the International Association for the Study of the Liver
Youcai ZhangCurtis D Klaassen
American Journal of Physiology. Gastrointestinal and Liver Physiology
Jaspreet S GujralHartmut Jaeschke
Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Jaspreet S GujralHartmut Jaeschke
© 2022 Meta ULC. All rights reserved