Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 20, Issue 2, Pages 352-357Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2014.04.001
Keywords
Tryptase; Protease-activated receptor 2; Bile duct ligation; Hepatic fibrosis
Categories
Funding
- Capital Medical University Basic-Clinical Research Project [JL1271]
Ask authors/readers for more resources
Protease-activated receptor (PAR) 2 is a G-protein-coupled receptor that is activated by mast cell tryptase. PAR-2 activation augments profibrotic pathways through the induction of extracellular matrix proteins. PAR-2 is widely expressed in hepatic stellate cells (HSCs), but the role of tryptase/PAR-2 interaction in liver fibrosis is unclear. We studied the development of bile duct ligation (BDL)-induced hepatic fibrosis in rats treated with mast cell tryptase inhibitor APC 366, and showed that APC 366 reduced hepatic fibrosis scores, collagen content and serum biochemical parameters. Reduced fibrosis was associated with decreased expression of PAR-2 and a-smooth muscle actin (a-SMA). Our findings demonstrate that mast cell tryptase induces PAR-2 activation to augment HSC proliferation and promote hepatic fibrosis in rats. Treatment with tryptase antagonists may be a novel therapeutic approach to prevent fibrosis in patients with chronic liver disease. (c) 2014 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available