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| Status |
Public on Sep 19, 2012 |
| Title |
Factor VII activating protease (FSAP) exerts antifibrotic effects in a mouse model of experimental liver fibrosis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
The dataset comprises 12 samples divided into four sample groups each representing a certain treatment group.
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| Contributor(s) |
Borkham-Kamphorst E, Bissels U, Bosio A, Weiskirchen R, Kanse SM |
| Citation(s) |
22989567 |
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| Submission date |
Feb 24, 2012 |
| Last update date |
Nov 01, 2017 |
| Contact name |
Ute Bissels |
| E-mail(s) |
ute.bissels@miltenyibiotec.de
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| Organization name |
Miltenyi Biotec GmbH
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| Department |
R&D
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| Street address |
Friedrich-Ebert-Str. 68
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| City |
Bergisch Gladbach |
| State/province |
NRW |
| ZIP/Postal code |
51429 |
| Country |
Germany |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA151821 |
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