title: Factor VII activating protease (FSAP) exerts anti-inflammatory and anti-fibrotic effects in liver fibrosis in mice and men.
abstract: OBJECTIVE
  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 α-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.
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, RWTH University Hospital, Aachen, Germany.
authors.forename: Erawan
authors.initials: E
authors.lastname: Borkham-Kamphorst
authors.forename: Henning W
authors.initials: HW
authors.lastname: Zimmermann
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Gassler
authors.forename: Ute
authors.initials: U
authors.lastname: Bissels
authors.forename: Andreas
authors.initials: A
authors.lastname: Bosio
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
authors.forename: Ralf
authors.initials: R
authors.lastname: Weiskirchen
authors.forename: Sandip M
authors.initials: SM
authors.lastname: Kanse
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D006505:Hepatitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000276:immunology*; D008103:Liver Cirrhosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012697:Serine Endopeptidases / Q000097:blood / Q000235:genetics / Q000276:immunology*; D059467:Transcriptome; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C520095:FSAP protein, mouse; C433550:HABP2 protein, human; D012697:Serine Endopeptidases