Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

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

Oncogene volume 22, pages 4380–4388 (2003)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Arora V, Knapp DC, Smith BL, Statdfield ML, Stein DA, Reddy MT, Weller DD and Iversen PL . (2000). Pharmacol. Exp. Ther., 292, 921–928.

  • Behrens A, Sibilia M. David JP, Mohle-Steinlein U, Tronche F, Schutz G and Wagner EF . (2002). EMBO J., 21, 1782–1790.

  • Cressman DE, Greenbaum LE, DeAngelis RA, Ciliberto G, Furth EE, Poli V and Taub R . (1996). Science, 274, 1379–1383.

  • de Moerlooze L, Spencer-Dene B, Revest J, Hajihosseini M, Rosewell I and Dickson C . (2000). Development, 127, 483–492.

  • Fausto N . (2000). J. Hepatol., 32, 19–31.

  • Housley RM, Morris CF, Boyle W, Ring B, Biltz R, Tarpley JE, Aukerman SL, Devine PL, Whitehead RH and Pierce GF . (1994). J. Clin. Invest., 94, 1764–1777.

  • Hu Z, Evarts RP, Fujio K, Marsden ER and Thorgeirsson SS . (1995). Cell Growth Differ., 6, 1019–1025.

  • Johnson DE and Williams LT . (1993). Adv. Cancer Res., 60, 1–41.

  • Jung J, Zheng M, Goldfarb M and Zaret KS . (1999). Science, 284, 1998–2003.

  • Kan M, Wu X, Wang F and McKeehan WL . (1999). J. Biol. Chem., 274, 15947–15952.

  • Korhonen J, Partanen J and Alitalo K . (1992). Int. J. Dev. Biol., 36, 323–329.

  • Loyer P, Ilyin G, Cariou S, Glaise D, Corlu A and Guguen-Guillouzo C . (1996). Prog Cell Cycle Res. 2, 37–47.

  • Lüdde T, Kubicka S, Plumpe J, Liedtke C, Manns MP and Trautwein C . (2001). Oncogene, 20, 5264–5278.

  • Marsden ER, Hu Z, Fujio K, Nakatsukasa H, Thorgeirsson SS and Evarts RP . (1992). Lab. Invest., 67, 427–433.

  • Nonogaki K, Pan XM, Moser AH, Staprans I, Feingold KR and Grunfeld C . (1995). Endocrinology, 136, 4278–4284.

  • Ornitz DM and Itoh N . (2001). Genome. Biol., 2, 3005 (reviews).

  • Peters K, Werner S, Liao X, Wert S, Whitsett J and Williams L . (1994). EMBO J., 13, 3296–3301.

  • Senaldi G, Shaklee CL, Simon B, Rowan CG, Lacey DL and Hartung T . (1998). Hepatology, 27, 1584–1591.

  • Strain AJ, McGuinness G, Rubin JS and Aaronson SA . (1994). Exp. Cell Res., 210, 253–259.

  • Suzuki M, Itoh T, Osada H, Rubin JS, Aaronson SA, Suzuki T, Koga N, Saito T and Mitsui Y . (1993). FEBS Lett., 328, 17–20.

  • Sweetser DA, Birkenmeier EH, Hoppe PC, McKeel DW and Gordon JI . (1988). Genes Dev., 2, 1318–1332.

  • Trautwein C, Rakemann T, Malek NP, Plumpe J, Tiegs G and Manns MP . (1998). J. Clin. Invest., 101, 1960–1969.

  • Ueno H, Gunn M, Dell K, Tseng Jr A and Williams LT . (1992). J. Biol. Chem., 267, 1470–1476.

  • Werner S, Smola H, Liao X, Longaker MT, Krieg T, Hofschneider PH and Williams LT . (1994). Science, 266, 819–822.

  • Werner S, Weinberg W, Liao X, Peters KG, Blessing M, Yuspa SH, Weiner RL and Williams LT . (1993). EMBO J., 12, 2635–2643.

  • Yamada Y, Webber EM, Kirillova I, Peschon JJ and Fausto N . (1997). Proc. Natl. Acad. Sci. USA, 94, 1441–1446.

  • Yu C, Wang F, Kan M, Jin C, Jones RB, Weinstein M, Deng CX and McKeehan WL . (2000). J. Biol. Chem., 275, 15482–15489.

Download references

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).

Author information

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

Authors
  1. Heike Steiling
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Torsten Wüstefeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Philippe Bugnon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Brauchle
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Reinhard Fässler
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Daniel Teupser
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joachim Thiery
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jeffrey I Gordon
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christian Trautwein
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sabine Werner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sabine Werner.

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

Keywords

This article is cited by

Search

Advanced search

Quick links