Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2017; 23(31): 5692-5699
Published online Aug 21, 2017. doi: 10.3748/wjg.v23.i31.5692
Cytoplasmic domain of tissue factor promotes liver fibrosis in mice
Virginia Knight, Dinushka Lourensz, Jorge Tchongue, Jeanne Correia, Peter Tipping, William Sievert
Virginia Knight, Dinushka Lourensz, Jorge Tchongue, Jeanne Correia, Peter Tipping, William Sievert, Centre for Inflammatory Diseases, Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria 3168, Australia
Virginia Knight, William Sievert, Gastroenterology and Hepatology Unit, Monash Health, Melbourne, Victoria 3168, Australia
Author contributions: Knight V, Lourensz D, Tchongue J and Correia J acquired and analysed data; Knight V, Sievert W and Tipping P designed the study, interpreted the data and contributed to writing of the article, editing, and reviewing; all authors approved the final version of the article.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Monash University Animal Ethics Committee (MMCB 2004/10).
Conflict-of-interest statement: The authors have no conflicts of interest to report.
Data sharing statement: All available data can be obtained by contacting the corresponding author.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: William Sievert, MD, FRACP, Professor, Director, Gastroenterology and Hepatology Unit, Monash Health, 246 Clayton Road, Melbourne, Victoria 3168, Australia. william.sievert@monash.edu
Telephone: +61-95943177 Fax: +61-95946250
Received: January 6, 2017
Peer-review started: January 9, 2017
First decision: March 16, 2017
Revised: May 9, 2017
Accepted: July 4, 2017
Article in press: July 4, 2017
Published online: August 21, 2017
Processing time: 224 Days and 22.1 Hours
Core Tip

Core tip: No effective anti-fibrotic therapies are available for patients with cirrhosis. PAR-2, a receptor that activates coagulation and inflammation, promotes hepatic fibrosis; whether tissue factor (TF), the primary initiator of the coagulation cascade, affects hepatic fibrosis is unknown. We found that deletion of the TF cytoplasmic domain reduces fibrosis through an effect on hepatic stellate cell activation, possibly mediated through reduced hepatic macrophage activation. Currently available direct thrombin inhibitors may be useful in preventing hepatic fibrosis while therapeutic targeting of the cytoplasmic domain of TF may be useful in patients with advanced liver disease, as its deletion does not alter coagulation.