gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Defining the role of Lipocalin 2/Lcn2 in liver regeneration

Meeting Abstract

  • Katrin Kienzl-Wagner - Medizinische Universität Innsbruck, Viszeral-, Transplantations- und Thoraxchirurgie, Innsbruck
  • Alexander Rupert Moschen - Medizinische Universität Innsbruck, Gastroenterologie und Hepatologie, Innsbruck
  • Sabine Geiger - Medizinische Universität Innsbruck, Gastroenterologie und Hepatologie, Innsbruck
  • Gerald Brandacher - Medizinische Universität Innsbruck, Viszeral-, Transplantations- und Thoraxchirurgie, Innsbruck
  • Felix Aigner - Medizinische Universität Innsbruck, Viszeral-, Transplantations- und Thoraxchirurgie, Innsbruck
  • Johann Pratschke - Medizinische Universität Innsbruck, Viszeral-, Transplantations- und Thoraxchirurgie, Innsbruck
  • Raimund Margreiter - Medizinische Universität Innsbruck, Viszeral-, Transplantations- und Thoraxchirurgie, Innsbruck
  • Herbert Tilg - Medizinische Universität Innsbruck, Gastroenterologie und Hepatologie, Innsbruck

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch613

DOI: 10.3205/11dgch613, URN: urn:nbn:de:0183-11dgch6130

Published: May 20, 2011

© 2011 Kienzl-Wagner et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

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Introduction: Liver resection in patients with primary and secondary hepatic tumours is limited by the fact that a sufficient amount of functional remnant liver has to be preserved. Maximization of liver regeneration represents a promising strategy to improve outcomes after extensive liver resection. Growing evidence suggests that lipocalin 2 has a role in regenerative processes.

Materials and methods: To establish the role of lipocalin 2 in liver regeneration lcn2+/+, lcn2+/- and lcn2-/- mice were subjected to 2/3 partial hepatectomy. Hepatic proliferation was measured by BrdU and PCNA immunohistochemistry. Hepatic lcn2 expression was analyzed by qRT-PCR and western blots. Serum levels of lcn2, Il-6, and TNF-α were determined by ELISA.

Results: Hepatic regeneration in lcn2+/+ mice was analyzed at 24, 48, 72 and 96h after partial hepatectomy. The peak of hepatic proliferation as indicated by the number of BrdU- and PCNA-positive cells was confirmed to be at 48h post surgery.

Analysis of hepatic lcn2 expression showed a 140-fold up-regulation only 24h after liver resection in lcn2+/+ animals with a stepwise reduction during the observation period (48h 15.7-fold, 72h 5.5-fold, 96h 5.8-fold). Western blots confirmed significant lcn2 protein over-expression 24h after partial hepatectomy. Also, serum lcn2 levels were significantly elevated upon liver resection.

To determine the biological relevance of lcn2 induction on liver regeneration, hepatocyte proliferation was analyzed in lcn2+/- and lcn2-/- mice 48h after partial hepatectomy. The number of BrdU- and PCNA-positive cells did not differ significantly between the groups. However, lcn2-/- animals exhibited a significantly elevated baseline liver regeneration (6.6-fold lcn2-/- vs lcn2+/+, p<0.05).

Conclusion: Up-regulation of lipocalin 2 after murine partial hepatectomy is striking but without significant impact on hepatocyte proliferation. Our results imply that lcn2 induction upon liver resection either constitutes a redundant pathway or simply displays an epiphenomenon.