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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 27, 2013 |
| Title |
Jnk1 in murine hepatic stellate cells is a crucial mediator of liver fibrogenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Hepatic fibrosis is a wound-healing response to chronic liver injury, which may result in cirrhosis and liver failure. The c-Jun N-terminal kinase-1 (JNK1) gene has been shown to be involved in liver fibrosis. Here, we aimed to investigate the molecular mechanism and identify the cell-type involved in mediating the JNK1-dependent effect on liver fibrogenesis Wild-type (WT), JNK1−/− and JNK1Δhepa (hepatocyte-specific deletion of JNK1) mice were subjected to bile duct ligation (BDL). Additionally, we performed bone marrow transplantations (BMT), isolated primary hepatic stellate cells (HSCs) and studied their activation in vitro. Serum markers of liver damage (liver transaminases, alkaline phosphatase and bilirubin) and liver histology revealed reduced injury in JNK1−/− compared to WT and JNK1Δhepa mice. Hepatocyte cell death and proliferation was reduced in JNK1−/− compared to WT and JNK1Δhepa. Parameters of liver fibrosis such as Sirius Red staining as well as Collagen IA1 and αSMA expression were down-regulated in JNK1−/− compared to WT and JNK1Δhepa livers, 4 weeks after BDL. To delineate the essential cell-type, we performed BMT of WT and JNK1-/- into JNK1-/- and WT mice, respectively. BMT experiments excluded bone marrow derived cells from having a major impact on the JNK1-dependent effect on fibrogenesis. Hence, we investigated primary HSCs from JNK1−/− livers showing reduced transdifferentiation compared with WT and JNK1Δhepa-derived HSCs. We conclude that JNK1 in HSCs plays a crucial role in hepatic fibrogenesis and thus represents a promising target for cell-directed treatment options for liver fibrosis.
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| Overall design |
Control (JNK1f/f), JNK1 null (JNK1-/-) and hepatocyte-specific JNK1 null (JNK1Δhepa) mice were subjected to control, acute and chronic injury, i.e. sham or bile-duct ligation for 48h or 28 days resp., whereafter gene expression profiles were determined.
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| Contributor(s) |
Zhao G, Hatting M, Nevzorova YA, Boekschoten MV, Drvarov O, Roskams T, Müller M, Cubero F, Trautwein C |
| Citation(s) |
24037431 |
| Submission date |
Aug 10, 2012 |
| Last update date |
Apr 18, 2017 |
| 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) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA172763 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE40041_RAW.tar |
107.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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