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Factor VII activating protease (FSAP) exerts anti-inflammatory and anti-fibrotic effects in liver fibrosis in mice and men.
- Source :
-
Journal of hepatology [J Hepatol] 2013 Jan; Vol. 58 (1), pp. 104-11. Date of Electronic Publication: 2012 Sep 16. - Publication Year :
- 2013
-
Abstract
- Background & Aims: Factor VII activating protease (FSAP) is a circulating serine protease produced in the liver. A single nucleotide polymorphism (G534E, Marburg I, MI-SNP) in the gene encoding FSAP (HABP2) leads to lower enzymatic activity and is associated with enhanced liver fibrosis in humans. FSAP is activated by damaged cells and its substrates include growth factors and hemostasis proteins.<br />Methods: We have investigated the progression of liver fibrosis in FSAP deficient mice and FSAP expression in human liver fibrosis.<br />Results: Serum FSAP concentrations declined in patients with end-stage liver disease, and hepatic FSAP expression was decreased in patients with advanced liver fibrosis and liver inflammation. Moreover, there was an inverse correlation between hepatic FSAP expression and inflammatory chemokines, chemokine receptors as well as pro-fibrotic mediators. Upon experimental bile duct ligation, FSAP(-/-) mice showed enhanced liver fibrosis in comparison to wild type mice, alongside increased expression of α-smooth muscle actin, collagen type I and fibronectin that are markers of stellate cell activation. Microarray analyses indicated that FSAP modulates inflammatory pathways.<br />Conclusions: Lower FSAP expression is associated with enhanced liver fibrosis and inflammation in patients with chronic hepatic disorders and murine experimental liver injury. This strengthens the concept that FSAP is a "protective factor" in liver fibrosis and explains why carriers of the Marburg I SNP have more pronounced liver fibrosis.<br /> (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Animals
Disease Models, Animal
Enzyme Activation genetics
Female
Hepatitis genetics
Hepatitis metabolism
Humans
Liver Cirrhosis genetics
Liver Cirrhosis metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Transgenic
Middle Aged
Polymorphism, Single Nucleotide genetics
RNA, Messenger metabolism
Serine Endopeptidases blood
Serine Endopeptidases genetics
Transcriptome
Young Adult
Hepatitis immunology
Liver enzymology
Liver immunology
Liver Cirrhosis immunology
Serine Endopeptidases immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1600-0641
- Volume :
- 58
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 22989567
- Full Text :
- https://doi.org/10.1016/j.jhep.2012.09.007