Page 153 - ebook HCC

EASL HCC SUMMITHCC SUMMIT
PROGRAMME AND ABSTRACTSAND ABSTRACTS
GENEVA, SWITZERLANDA, SWITZERLAND
150 PROGRAMME GENEV EASL 151
151
150
FEBRUAR
FEBRUARY 13 - 16, 2014Y 13 - 16, 2014
Poster Board Number B40
THE ROLE OF GROWTH HORMONE RECEPTOR
IN LIVER FIBROSIS AND CANCER

Patricia Stiedl , Leander Blaas , Viktoria Stanek , Jasmin Svinka , Results: Our results indicate that Ghr ;Mdr2 mice show deregulation of bile acid
2
1
3
-/-
1
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Robert Mc Mahon , Gernot Zollner , Thierry Claudel , Mathias Mueller , homeostasis and increased serum markers associated with inflammation and fibrosis. Bile
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Wolfgang Mikulits , Harald Esterbauer , Robert Eferl , Johannes Haybeack , duct proliferation and extensive collagen deposition were also observed in Ghr ;Mdr2
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-/-
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7
-/-
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Michael Trauner , Emilio Casanova 1 compared to Mdr2 mice, suggesting that Ghr ;Mdr2 developed a severe liver fibrosis
-/-
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1 Ludwig Boltzmann Institute for Cancer Research, Vienna, Austria, phenotype. Additionally, a greater down regulation of the hepato-protective genes Hnf6,
-/-
2 Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, Sweden, Egfr and Igf-1 accompanied by increased apoptosis was seen in Ghr ;Mdr2 compared to
-/-
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3 Department of Internal Medicine I, Institute for Cancer Research, Medical University of control mice. Moreover, single knockout mice (Ghr ) developed bile infacts when fed with
Vienna, Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology 1% cholic acid compared to Wt controls, indicating that hepatocytes upon loss of GHR
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-/-
and Hepatology, Department of Internal Medicine III, Medical University of Vienna, become more susceptible to toxic bile acid accumulation. Surprisingly, Ghr ;Mdr2 mice
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Vienna, Division of Gastroenterology and Hepatology, Department of Internal Medicine, showed a significant decrease in tumour incidence compared to Mdr2 mice despite their
Medical University of Graz, Graz, Biomodels Austria, Institute of Animal Breeding and severe fibrotic phenotype indicating that loss of GHR signalling may slow the progression
6
Genetics, University of Veterinary Medicine Vienna, from fibrosis/cirrhosis to cancer in the liver.
7 Department of Laboratory Medicine, Medical University of Vienna, Vienna,
8 Institute of Pathology, Medical University of Graz, Graz, Austria Conclusions: These findings suggest that loss of GHR signalling severely increased liver
fibrosis in a mouse model of inflammatory cholestasis, signifying the possible therapeutic

BASIC POSTER ABSTRACTS Introduction: Recently, growth hormone resistance and low serum levels of insulin BASIC POSTER ABSTRACTS
value of this pathway in the development of liver fibrosis treatments.
Corresponding author’s e-mail: Patricia.Stiedl@lbicr.lbg.ac.at
growth factor (IGF-1) have been associated with liver cirrhosis in humans, indicating a
role for growth hormone receptor, which itself controls various cellular functions including
the transcription of IGF-1 through signal transducer and activator of transcription 5 (Stat5)
signalling.
Aims: In order to elucidate whether the growth hormone receptor (GHR) plays an active
role in the establishment of fibrosis liver diseases or rather happens to be a major
consequence of this illness, we crossed mice lacking the Ghr/bp gene (Ghr ) with a
-/-
mouse model of inflammatory cholestasis and liver fibrosis, the Mdr2 knockout mouse
(Mdr2 ).
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Methodology: Serum parameters and bile acid levels were analysed. Additionally
histological stainings, western blotting and RT-PCRs were conducted to gain mechanistic
insights.