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Title: Factor VII activating protease (FSAP) exerts antifibrotic effects in a mouse model of experimental liver fibrosis      
dateReleased:
09-19-2012
description:
Background and Rationale: 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. FSAP is activated by damaged cells and its substrates include growth factors and haemostasis proteins. We have investigated the progression of liver fibrosis in FSAP deficient mice. Results: Wild type (WT) or FSAP-/- mice were subjected to bile duct ligation (BDL) and assessment of liver fibrosis. FSAP-/- mice showed enhanced liver fibrosis and accumulation of extracellular matrix as determined by Sirius Red staining and hydroxyproline content. FSAP deficient mice exhibited stronger injury as determined by higher necrosis in the liver and circulating liver enzymes. This correlated with expression of markers like α-smooth muscle actin, collagen and fibronectin that are markers of stellate cell activation. FSAP-deficient mice exhibited higher expression of PDGF-BB as well as PDGFRβ that are strong activators of liver fibrosis. In order to gain more insight into this difference microarray analysis was performed and the pattern of gene expression in WT vs. FSAP-/- mice would indicate that FSAP modulates the inflammatory /immune system. Conclusions: The results with FSAP-/- mice correlates with the human situation where lower FSAP activity, due to the MI SNP, is associated with enhanced liver fibrosis. This strengthens the concept that FSAP is a “protective factor” in liver fibrosis. A probable mechanism for this effect is likely to be related to the role of FSAP in the regulation of fibrosis/ inflammation-related processes n the liver. The dataset comprises 12 samples divided into four sample groups each representing a certain treatment group.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-36066
refinement:
raw
alternateIdentifiers:
36066
keywords:
functional genomics
dateModified:
09-24-2012
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-GEOD-11202
name:
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version)
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-36066/E-GEOD-36066.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-36066/E-GEOD-36066.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36066
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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