Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Lemberger, UJ; Fuchs, CD; Karer, M; Haas, S; Stojakovic, T; Schöfer, C; Marschall, HU; Wrba, F; Taketo, MM; Egger, G; Trauner, M; Österreicher, CH.
Hepatocyte specific expression of an oncogenic variant of β-catenin results in cholestatic liver disease.
Oncotarget. 2016; 7(52):86985-86998
Doi: 10.18632/oncotarget.13521
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- Co-authors Med Uni Graz
- Stojakovic Tatjana
- Trauner Michael
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- Abstract:
- The Wnt/β-catenin signaling pathway plays a crucial role in embryonic development, tissue homeostasis, wound healing and malignant transformation in different organs including the liver. The consequences of continuous β-catenin signaling in hepatocytes remain elusive. Livers of Ctnnb1CA hep mice were characterized by disturbed liver architecture, proliferating cholangiocytes and biliary type of fibrosis. Serum ALT and bile acid levels were significantly increased in Ctnnb1CA hep mice. The primary bile acid synthesis enzyme Cyp7a1 was increased whereas Cyp27 and Cyp8b1 were reduced in Ctnnb1CA hep mice. Expression of compensatory bile acid transporters including Abcb1, Abcb4, Abcc2 and Abcc4 were significantly increased in Ctnnb1CA hep mice while Ntcp was reduced. Accompanying changes of bile acid transporters favoring excretion of bile acids were observed in intestine and kidneys of Ctnnb1CA hep mice. Additionally, disturbed bile acid regulation through the FXR-FGF15-FGFR4 pathway was observed in mice with activated β-catenin. Mice with a loxP-flanked exon 3 of the Ctnnb1 gene were crossed to Albumin-Cre mice to obtain mice with hepatocyte-specific expression of a dominant stable form of β-catenin (Ctnnb1CA hep mice). Ctnnb1CA hep mice were analyzed by histology, serum biochemistry and mRNA profiling. Expression of a dominant stable form of β-catenin in hepatocytes results in severe cholestasis and biliary type fibrosis.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Bile Acids and Salts - metabolism
- Cholestanetriol 26-Monooxygenase - genetics
- Cholestasis - etiology
- Cholesterol 7-alpha-Hydroxylase - genetics
- Hepatocytes - metabolism
- Liver Cirrhosis, Biliary - etiology
- Mice -
- Mice, Inbred C57BL -
- Signal Transduction - physiology
- beta Catenin - physiology
- Find related publications in this database (Keywords)
- beta-catenin
- bile acids
- cholestasis
- biliary fibrosis
- liver cancer