Factor VII activating protease (FSAP) exerts anti-inflammatory and anti-fibrotic effects in liver fibrosis in mice and men

被引：26

作者：

Borkham-Kamphorst, Erawan ^{[1
]}

Zimmermann, Henning W. ^{[2
]}

Gassler, Nikolaus ^{[3
]}

Bissels, Ute ^{[4
]}

Bosio, Andreas ^{[4
]}

Tacke, Frank ^{[2
]}

Weiskirchen, Ralf ^{[1
]}

Kanse, Sandip M. ^{[5
,6
]}

机构：

[1] RWTH Univ Hosp, Inst Clin Chem & Pathobiochem, D-52074 Aachen, Germany

[2] RWTH Univ Hosp, Dept Med 3, D-52074 Aachen, Germany

[3] RWTH Univ Hosp, Inst Pathol, D-52074 Aachen, Germany

[4] Miltenyi Biotec GmbH, D-51429 Bergisch Gladbach, Germany

[5] Univ Oslo, Inst Basic Med Sci, Oslo, Norway

[6] Univ Giessen, Inst Biochem, D-35390 Giessen, Germany

来源：

JOURNAL OF HEPATOLOGY | 2013年 / 58卷 / 01期

关键词：

Liver fibrosis; HABP2; Marburg I SNP; HYALURONAN-BINDING PROTEIN; HEPATIC-FIBROSIS; INHIBITION; PROLIFERATION; PATHOGENESIS; INFLAMMATION; POLYMORPHISM; PROTEOLYSIS; INJURY; G534E;

D O I：

10.1016/j.jhep.2012.09.007

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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. Methods: We have investigated the progression of liver fibrosis in FSAP deficient mice and FSAP expression in human liver fibrosis. 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 a-smooth muscle actin, collagen type I and fibronectin that are markers of stellate cell activation. Microarray analyses indicated that FSAP modulates inflammatory pathways. 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. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

引用

页码：104 / 111

页数：8

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