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Autoimmune, Cholestatic and Biliary Disease
Article first published online: 7 APR 2011
Copyright © 2011 American Association for the Study of Liver Diseases
Volume 53, Issue 4, pages 1287–1297, April 2011
How to Cite
Kireva, T., Erhardt, A., Tiegs, G., Tilg, H., Denk, H., Haybaeck, J., Aigner, E., Moschen, A., Distler, J. H., Schett, G. and Zwerina, J. (2011), Transcription factor Fra-1 induces cholangitis and liver fibrosis . Hepatology, 53: 1287–1297. doi: 10.1002/hep.24175
Supported by the Interdisziplinäres Zentrum für Klinische Forschung Erlangen Project A34 (to G.S. and J.Z.), Deutsche Forschungsgemeinschaft Grant FOR 661 (to G.S.) and SFB 423 (to J.Z. and G.S.) and the European Union projects Masterswitch, Adipoa and Kinacept.
Potential conflict of interest: Nothing to report.
- Issue published online: 7 APR 2011
- Article first published online: 7 APR 2011
- Accepted manuscript online: 10 JAN 2011 01:03PM EST
- Manuscript Accepted: 21 DEC 2010
- Manuscript Received: 12 MAY 2010
- Interdisziplinäres Zentrum für Klinische Forschung Erlangen Project A34
- Deutsche Forschungsgemeinschaft. Grant Numbers: FOR 661, SFB 423
- European Union projects Masterswitch, Adipoa and Kinacept
Additional Supporting Information may be found in the online version of this article.
|HEP_24175_sm_suppinfofigure1.tif||715K||Supporting Figure 1. Chemokine and chemokine receptor expression profile of liver tissue Changes of chemokines and their receptors were determined in livers of 3 fra-1tg vs. wildtype animals at the age of 6 weeks using RT2 Profiler PCR Array. Results are presented as x-fold increase vs. wildtype mice.|
|HEP_24175_sm_suppinfofigure2.tif||11210K||Supporting Figure 2. Inflammatory infiltration in the liver of fra-1tg mice The composition of the portal inflammatory infiltrates of fra-1tg mice was investigated by immunohistochemistry. Neutrophils, T cells (CD3+ cells) and B cells (CD45R+ cells) were predominantly found in the portal fields. Staining for macrophages (F4/80+ cells) showed presence of Kupffer cells in the perisinusidal spaces. Representative images are shown (magnification 100times;).|
|HEP_24175_sm_suppinfofigure3.tif||953K||Supporting Figure 3: Increased profibrogenic gene expression in fra-1tg mice Relative hepatic mRNA transcript levels of the profibrotic genes PDGF-A and PDGF-C and the profibrolitic genes MMP-9, MMP-2 and TIMP-1 in fra-1tg and wildtype mice were measured by quantitative real-time PCR. Results are expressed as mean ± SEM (n-4-5/group) and in arbitrary units relative to β-actin mRNA. Data are presented as an x-fold increase vs. the corresponding wildtype controls. *P<0.05 compared to wildtype controls of the corresponding age.|
|HEP_24175_sm_suppinfofigure4.tif||2610K||Supporting Figure 4: Binding of Fra-1 to the promoters of tgfβ1, pdgf-b and pdgf-d genes Binding activity of the transcription factor Fra-1 to the promoters of tgfβ1, pdgf-b and pdgf-d genes was determined by ChIP assay. We analysed 2000 bp sequences (-2000/+1) of tgfβ1, pdgf-b and –d promoters and found 2, 3 and 1 possible binding sites for the transcription factor AP-1, respectively. Binding activity of Fra-1 in wildtype and transgenic cholangiocytes was demonstrated by PCR. As negative control an IgG antibody was used.|
|HEP_24175_sm_suppinfofigure5.tif||1799K||Supporting Figure 5: Matrix accumulation in fra-1tg x rag2-/- mice Accumulation of matrix proteins rag2-/-, fra-1tg x rag2+/- and fra-1tg x rag2-/- mice was determined by measurement of fibrosis area in 5 high power fields. Further, expression of collagen genes was determined by quantitative real time PCR. Gene expression and fibrosis area increase are presented as x-fold vs. rag2 -/-control mice.|
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