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Series GSE40041 Query DataSets for GSE40041
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
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.
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.
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
Organization name Wageningen University
Department Div. Human Nutrition & Health
Lab Nutrition, Metabolism & Genomics Group
Street address HELIX, Stippeneng 4
City Wageningen
ZIP/Postal code NL-6708WE
Country Netherlands
Platforms (1)
GPL11533 [MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version]
Samples (24)
GSM984168 Con BDL 28d rep1
GSM984169 Con BDL 28d rep2
GSM984170 Con BDL 28d rep3
BioProject PRJNA172763

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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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