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Fibroblast growth factor receptor signalling is crucial for liver homeostasis and regeneration

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Abstract

Several growth factors have been suggested to play a crucial role in liver regeneration, but a functional proof is still missing. Since fibroblast growth factors are important for the initiation of mammalian liver development, we determined the roles of these mitogens in liver repair by targeted expression of a dominant-negative fibroblast growth factor receptor (FGFR) in hepatocytes of transgenic mice. The liver of young animals appeared histologically normal, and liver function was not obviously impaired. In aged transgenic mice, the frequency of fatty liver development was strongly increased compared to control animals. Following partial hepatectomy, transgenic mice showed markedly reduced hepatocyte proliferation because of an arrest in the late G1 phase of the cell cycle. These data demonstrate a key role of FGFR signalling in repair after liver injury.

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Acknowledgements

We thank Dr P Möller, Ulm, Germany and Dr R Wanke, Munich, Germany, for help and advice with the liver histology, and Dr Clive Dickson, London, UK, for critically reading the manuscript. This work was supported by grants from the Human Frontier Science Program (to SW), the Swiss National Science Foundation (Grant No. 31-61358.00 to SW) and the Deutsche Forschungsgemeinschaft (SFB 566, project B8 to CT).

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Authors and Affiliations

  1. Institute of Cell Biology, ETH Zürich, Hönggerberg, Zürich, CH-8093, Switzerland

    Heike Steiling, Philippe Bugnon & Sabine Werner

  2. Department of Gastroenterology and Hepatology, Medizinische Hochschule Hannover, Hannover, D-30625, Germany

    Torsten Wüstefeld & Christian Trautwein

  3. Novartis Pharma AG, Basel, CH-4002, Switzerland

    Maria Brauchle

  4. Max-Planck-Institute of Biochemistry, Am Klopferspitz 18a, Martinsried, D-82152, Germany

    Reinhard Fässler

  5. Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Universitätsklinikum Leipzig, Leipzig, D-04103, Germany

    Daniel Teupser & Joachim Thiery

  6. Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, 63110, MO, USA

    Jeffrey I Gordon

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  1. Heike Steiling
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  2. Torsten Wüstefeld
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  3. Philippe Bugnon
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  4. Maria Brauchle
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  5. Reinhard Fässler
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  7. Joachim Thiery
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  8. Jeffrey I Gordon
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  9. Christian Trautwein
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  10. Sabine Werner
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Correspondence to Sabine Werner.

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Steiling, H., Wüstefeld, T., Bugnon, P. et al. Fibroblast growth factor receptor signalling is crucial for liver homeostasis and regeneration. Oncogene 22, 4380–4388 (2003). https://doi.org/10.1038/sj.onc.1206499

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  • DOI: https://doi.org/10.1038/sj.onc.1206499

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