Liver fibrosis is driven by protease-activated receptor-1 expressed by hepatic stellate cells in experimental chronic liver injury.

Research and Practice in Thrombosis and Haemostasis
Lauren G PooleJames P Luyendyk

Abstract

Blood coagulation protease activity is proposed to drive hepatic fibrosis through activation of protease-activated receptors (PARs). Whole-body PAR-1 deficiency reduces experimental hepatic fibrosis, and in vitro studies suggest a potential contribution by PAR-1 expressed by hepatic stellate cells. However, owing to a lack of specific tools, the cell-specific role of PAR-1 in experimental hepatic fibrosis has never been formally investigated. Using a novel mouse expressing a conditional PAR-1 allele, we tested the hypothesis that PAR-1 expressed by hepatic stellate cells contributes to hepatic fibrosis. PAR-1flox/flox mice were crossed with mice expressing Cre recombinase controlled by the lecithin retinol acyltransferase (LRAT) promoter, which induces recombination in hepatic stellate cells. Male PAR-1flox/flox/LRATCre and PAR-1flox/flox mice were challenged twice weekly with carbon tetrachloride (CCl4, 1 mL/kg i.p.) for 6 weeks to induce liver fibrosis. PAR-1 mRNA levels were reduced (>95%) in hepatic stellate cells isolated from PAR-1flox/flox/LRATCre mice. Hepatic stellate cell activation was evident in CCl4-challenged PAR-1flox/flox mice, indicated by increased α-smooth muscle actin labeling and induction of several profib...Continue Reading

References

Jun 1, 1978·Archivum Histologicum Japonicum = Nihon Soshikigaku Kiroku·L C JunqueiraR Brentani
Jul 12, 1996·The Journal of Biological Chemistry·B D BlackhartR M Scarborough
Aug 26, 1998·Nature·M L KahnS R Coughlin
Feb 28, 2002·Journal of Hepatology·Marianna D A GaçaR Christopher Benyon
Dec 31, 2002·American Journal of Physiology. Cell Physiology·Michelle L SeymourWallace K MacNaughton
Feb 28, 2003·The Journal of Pharmacology and Experimental Therapeutics·Bryan L CoppleRobert A Roth
Feb 10, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Stefano FiorucciGiuseppe Cirino
Oct 14, 2004·Gut·J Gillibert DuplantierJ Rosenbaum
Dec 2, 2004·The European Respiratory Journal·Q FangS I Rennard
Sep 30, 2005·Virchows Archiv : an International Journal of Pathology·Anne RullierJean Rosenbaum
May 9, 2007·Gastroenterology·Samuele De MinicisRobert F Schwabe
Oct 27, 2007·American Journal of Physiology. Gastrointestinal and Liver Physiology·Anne RullierJean Rosenbaum
May 20, 2008·Journal of Thrombosis and Haemostasis : JTH·Q M AnsteeM R Thursz
Jan 20, 2009·Clinics in Liver Disease·Quentin M AnsteeMark R Thursz
Nov 3, 2010·The American Journal of Pathology·Bradley P SullivanJames P Luyendyk
May 17, 2011·Clinics and Research in Hepatology and Gastroenterology·Quentin M AnsteeMark R Thursz
Sep 24, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Leila M SevignyAthan Kuliopulos
Nov 19, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Virginia KnightWilliam Sievert
Dec 17, 2011·World Journal of Gastroenterology : WJG·Nitsan MaharshakRan Oren
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Jan 10, 2013·Biochimica Et Biophysica Acta·Paul F Mercer, Rachel C Chambers
Mar 19, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Akie MochizukiBryan L Copple
May 27, 2014·Frontiers in Endocrinology·Peishen ZhaoNigel W Bunnett
Jul 24, 2014·Physiological Reports·Jonathan M StreetRobert A Star
Oct 30, 2014·Journal of Thrombosis and Haemostasis : JTH·N JoshiJ P Luyendyk
Nov 28, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael J V WhiteRichard H Gomer
Dec 19, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Paul A GurbelAthan Kuliopulos
Dec 22, 2015·Journal of Hepatology·Federica CeriniJuan Carlos García-Pagán
Sep 9, 2016·Journal of Biochemical and Molecular Toxicology·Nikita JoshiJames P Luyendyk
Sep 11, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rance NaultJames P Luyendyk
Feb 1, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Marina VilasecaJoan Carles García-Pagán
May 22, 2017·Toxicology and Applied Pharmacology·Nikita JoshiJames P Luyendyk
May 4, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Asmita PantJames P Luyendyk
May 10, 2018·BMC Gastroenterology·Ameet DharMark R Thursz
Oct 6, 2018·Digestive Diseases and Sciences·Kuei-Chuan LeeHan-Chieh Lin
Nov 12, 2018·Journal of Thrombosis and Haemostasis : JTH·L G PooleJ P Luyendyk

❮ Previous
Next ❯

Citations

Jun 20, 2021·Laboratory Investigation; a Journal of Technical Methods and Pathology·Theresa GreimelAxel Schlagenhauf

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
PCR

Software Mentioned

ImageJ Fiji
Visiopharm
OlyVIA

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

Related Papers

Italian Journal of Gastroenterology and Hepatology
A Lang, D A Brenner
Progress in Liver Diseases
S L Friedman
Ugeskrift for laeger
Camilla Nøjgaard, Jens H Henriksen
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology
Wei-feng YangYi-ping Jiang
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology
J Zhao, J Cheng
© 2021 Meta ULC. All rights reserved