Inverse agonist of ERRγ reduces cannabinoid receptor type 1-mediated induction of fibrinogen synthesis in mice with a high-fat diet-intoxicated liver

Archives of Toxicology
Yaochen ZhangHueng-Sik Choi

Abstract

Upon liver intoxication with malnutrition or high-fat diet feeding, fibrinogen is synthesized by hepatocytes and secreted into the blood in human and mouse. Its primary function is to occlude blood vessels upon damage and thereby stop excessive bleeding. High fibrinogen levels may contribute to the development of pathological thrombosis, which is one mechanism linking fatty liver disease with cardiovascular disease. Our previous results present ERRγ as key regulator of hepatocytic fibrinogen gene expression in human. In a therapeutic approach, we now tested ERRγ inverse agonist GSK5182 as regulator of fibrinogen levels in mouse hyperfibrinogenemia caused by diet-induced obesity and in mouse hepatocytes. ACEA, a CB1R agonist, up-regulated transcription of mouse fibrinogen via induction of ERRγ, whereas knockdown of ERRγ attenuated the effect of ACEA (10 µM) on fibrinogen expression in AML12 mouse hepatocytes. Deletion analyses of the mouse fibrinogen γ (FGG) gene promoter and ChIP assays revealed binding sites for ERRγ on the mouse FGG promoter. ACEA or adenovirus ERRγ injection induced FGA, FGB and FGG mRNA and protein expression in mouse liver, while ERRγ knockdown with Ad-shERRγ attenuated ACEA-mediated induction of fibrinoge...Continue Reading

References

Jun 27, 1983·Annals of the New York Academy of Sciences·D G Ritchie, G M Fuller
Aug 23, 1984·The New England Journal of Medicine·L WilhelmsenG Tibblin
Oct 24, 1997·Nature·A M BrzozowskiM Carlquist
Feb 11, 1999·The New England Journal of Medicine·C Gabay, I Kushner
Jun 18, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Monica AcevedoDennis L Sprecher
May 17, 2003·The Journal of Biological Chemistry·Eiko SakaoMasaki Takiguchi
Aug 5, 2003·The Journal of Clinical Investigation·Daniela CotaUberto Pagotto
Dec 17, 2003·Journal of Thrombosis and Haemostasis : JTH·A van Hylckama Vlieg, F R Rosendaal
Nov 27, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jeffrey D BrowningHelen H Hobbs
Oct 13, 2005·JAMA : the Journal of the American Medical Association·UNKNOWN Fibrinogen Studies CollaborationA Wood
Nov 26, 2005·Bioorganic & Medicinal Chemistry Letters·Esther Y H ChaoWilliam J Zuercher
May 11, 2006·The Journal of Clinical Endocrinology and Metabolism·Isabel MatiasVincenzo Di Marzo
May 26, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Magali Gary-BoboMohammed Bensaid
Oct 4, 2007·Gut·Stephen A Harrison, Christopher Paul Day
Mar 6, 2010·The AAPS Journal·Vishnudutt PurohitDavid Shurtleff
Jun 24, 2010·Blood·Alexandre FortMarguerite Neerman-Arbez
Oct 21, 2010·Seminars in Liver Disease·Ariel E Feldstein
Feb 19, 2011·International Journal of Molecular Medicine·Mako ToyodaMunechika Enjoji
May 3, 2012·The Journal of Biological Chemistry·Don-Kyu KimHueng-Sik Choi
Jun 16, 2012·International Journal of Hepatology·Munechika EnjojiMakoto Nakamuta
Feb 18, 2017·Trends in Endocrinology and Metabolism : TEM·Jagannath MisraHueng-Sik Choi

❮ Previous
Next ❯

Citations

Jul 30, 2019·Pharmaceutical Patent Analyst·Hermann Am Mucke

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
transfection
transfections
ELISA
ChIP
PCR
immunoprecipitation

Related Concepts

Related Feeds

Cardiovascular Disease Pathophysiology

Cardiovascular disease involves several different processes that contribute to the pathological mechanism, including hyperglycemia, inflammation, atherosclerosis, hypertension and more. Vasculature stability plays a critical role in the development of the disease. Discover the latest research on cardiovascular disease pathophysiology here.

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.