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| Status |
Public on Feb 18, 2009 |
| Title |
c-Met confers protection against chronic liver tissue damage and fibrosis progression after bile-duct-ligation in mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The HGF/c-Met system is an essential inducer of hepatocyte growth and proliferation. Although a fundamental role for the HGF receptor c-Met has been demonstrated in acute liver regeneration its cell specific role in hepatocytes during chronic liver injury and fibrosis progression has not been determined yet. In order to better characterize the role of c-Met in hepatocytes we generated a hepatocyte-specific c-Met knockout mouse (c-Met∆hepa) using the Cre-loxP system and studied its relevance after bile-duct ligation. Two strategies for c-Met deletion in hepatocytes were tested. Early deletion during embryonic development was lethal, while post-natal Cre-expression was successful leading to the generation of viable c-Met∆hepa mice. Bile-duct ligation in these mice resulted in extensive necrosis and lower proliferation rates of hepatocytes. Gene array analysis of c-Met∆hepa mice revealed a significant reduction of anti-apoptotic genes in c-Met deleted hepatocytes. These findings could be functionally tested as c-Met∆hepa mice showed a stronger apoptotic response after bile-duct ligation and Jo-2 stimulation. This phenotype was associated with increased expression of pro-inflammatory cytokines (TNF-a and IL-6) and an enhanced recruitment of neutrophils. Activation of these mechanisms triggered a stronger pro-fibrogenic response as evidenced by increased TGF-b1, a-SMA, collagen-1a mRNA expression and enhanced collagen-fiber staining in c-Met∆hepa mice.
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| Overall design |
For gene array analysis c-MetDhepa and c-MetloxP/loxP controls were stimulated for 2 hours with 2µg recombinant mouse HGF.Three animals per group were treated in parallel, before and after i.p. injection of recombinant HGF or NaCl.
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| Contributor(s) |
Giebeler A, Klein C, Boekschoten MV, Borowiak M, Birchmeier C, Gassler N, Müller M, Trautwein C, Streetz KL |
| Citation(s) |
19208365 |
| Submission date |
Dec 16, 2008 |
| Last update date |
Aug 20, 2013 |
| Contact name |
Guido Hooiveld |
| E-mail(s) |
guido.hooiveld@wur.nl
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| Organization name |
Wageningen University
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| Department |
Div. Human Nutrition & Health
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| Lab |
Nutrition, Metabolism & Genomics Group
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| Street address |
HELIX, Stippeneng 4
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| City |
Wageningen |
| ZIP/Postal code |
NL-6708WE |
| Country |
Netherlands |
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| Platforms (1) |
| GPL7546 |
Affymetrix GeneChip Mouse Genome 430 2.0 Array [CDF: Mm_ENTREZG_10] |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA112489 |
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