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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2010

Authors: Blaas, L; Kornfeld, JW; Schramek, D; Musteanu, M; Zollner, G; Gumhold, J; van Zijl, F; Schneller, D; Esterbauer, H; Egger, G; Mair, M; Kenner, L; Mikulits, W; Eferl, R; Moriggl, R; Penninger, J; Trauner, M; Casanova, E

Title: Disruption of the growth hormone--signal transducer and activator of transcription 5--insulinlike growth factor 1 axis severely aggravates liver fibrosis in a mouse model of cholestasis.

Source: Hepatology. 2010; 51(4):1319-1326



Authors Vetmeduni Vienna:

Kenner Lukas
Moriggl Richard


Abstract:
Growth hormone (GH) resistance and low serum levels of insulinlike growth factor 1 (IGF-1) are common features in human liver fibrosis and cirrhosis. Signal transducer and activator of transcription 5 (STAT5) controls several vital functions in the liver, including GH-mediated transcription of IGF-1. To investigate the role of STAT5 in liver fibrogenesis, we specifically deleted the Stat5a/b locus both in hepatocytes and cholangiocytes in the multidrug resistance gene 2 knockout (Mdr2(-/-)) mouse model of cholestasis. Double knockout mice develop an early and severe liver fibrosis phenotype, accompanied by perturbed expression of key regulators of bile acid homeostasis. Deletion of Stat5 resulted in GH resistance, and IGF-1 levels in serum were undetectable. We could observe reduced expression of important hepatoprotective genes, such as epidermal growth factor receptor (Egfr), hepatocyte nuclear factor 6 (Hnf6), prolactin receptor (Prlr), and leukemia inhibitory factor receptor (Lifr) as well as increased numbers of apoptotic hepatocytes.

Keywords Pubmed: ATP Binding Cassette Transporter, Subfamily B/physiology
Animals
Apoptosis
Cholestasis/complications*
Disease Models, Animal
ErbB Receptors/genetics
Growth Hormone/physiology*
Hepatocyte Nuclear Factor 6/genetics
Insulin-Like Growth Factor I/physiology*
Liver Cirrhosis, Experimental/etiology*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Phenotype
STAT5 Transcription Factor/physiology*
Signal Transduction


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