Title |
Protease‐activated receptor 2 promotes experimental liver fibrosis in mice and activates human hepatic stellate cells
|
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Published in |
Hepatology, January 2012
|
DOI | 10.1002/hep.24784 |
Pubmed ID | |
Authors |
Virginia Knight, Jorge Tchongue, Dinushka Lourensz, Peter Tipping, William Sievert |
Abstract |
Protease-activated receptor (PAR) 2 is a G-protein-coupled receptor that is activated after proteolytic cleavage by serine proteases, including mast cell tryptase and activated coagulation factors. PAR-2 activation augments inflammatory and profibrotic pathways through the induction of genes encoding proinflammatory cytokines and extracellular matrix proteins. Thus, PAR-2 represents an important interface linking coagulation and inflammation. PAR-2 is widely expressed in cells of the gastrointestinal tract, including hepatic stellate cells (HSCs), endothelial cells, and hepatic macrophages; however, its role in liver fibrosis has not been previously examined. We studied the development of CCl(4) -induced liver fibrosis in PAR-2 knockout mice, and showed that PAR-2 deficiency reduced the progression of liver fibrosis, hepatic collagen gene expression, and hydroxyproline content. Reduced fibrosis was associated with decreased transforming growth factor beta (TGFβ) gene and protein expression and decreased matrix metalloproteinase 2 and tissue inhibitor of matrix metalloproteinase 1 gene expression. In addition, PAR-2 stimulated activation, proliferation, collagen production, and TGFβ protein production by human stellate cells, indicating that hepatic PAR-2 activation increases profibrogenic cytokines and collagen production both in vivo and in vitro. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Czechia | 1 | 2% |
Unknown | 43 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 9 | 20% |
Student > Master | 8 | 18% |
Researcher | 7 | 16% |
Student > Bachelor | 4 | 9% |
Student > Postgraduate | 3 | 7% |
Other | 6 | 14% |
Unknown | 7 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 13 | 30% |
Agricultural and Biological Sciences | 9 | 20% |
Biochemistry, Genetics and Molecular Biology | 6 | 14% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 5% |
Immunology and Microbiology | 2 | 5% |
Other | 3 | 7% |
Unknown | 9 | 20% |