The role of lipocalin-2 in liver regeneration

Authors

  • Katrin Kienzl-Wagner,

    1. Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Innsbruck Medical University, Innsbruck, Austria
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    • Both authors contributed equally to this study.
  • Alexander R. Moschen,

    1. Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck Medical University, Innsbruck, Austria
    2. Department of Internal Medicine I (Gastroenterology, Endocrinology & Metabolism), Innsbruck Medical University, Innsbruck, Austria
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    • Both authors contributed equally to this study.
  • Sabine Geiger,

    1. Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck Medical University, Innsbruck, Austria
    2. Department of Internal Medicine I (Gastroenterology, Endocrinology & Metabolism), Innsbruck Medical University, Innsbruck, Austria
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  • Alexandra Bichler,

    1. Department of Internal Medicine I (Gastroenterology, Endocrinology & Metabolism), Innsbruck Medical University, Innsbruck, Austria
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  • Felix Aigner,

    1. Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Innsbruck Medical University, Innsbruck, Austria
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  • Gerald Brandacher,

    1. Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Johann Pratschke,

    1. Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Innsbruck Medical University, Innsbruck, Austria
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  • Herbert Tilg

    Corresponding author
    1. Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck Medical University, Innsbruck, Austria
    2. Department of Internal Medicine I (Gastroenterology, Endocrinology & Metabolism), Innsbruck Medical University, Innsbruck, Austria
    • Correspondence

      Herbert Tilg, MD, Department of Internal Medicine I, Innsbruck Medical University, Anichstrasse 35, Innsbruck 6020, Austria

      Tel: +43 512 504 23540

      Fax: +43 512 504 23538

      e-mail: herbert.tilg@i-med.ac.at

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Abstract

Background & Aims

Various immune mediators such as interleukin-6 (IL-6) have been implicated in the process of liver regeneration. Lipocalin-2 (LCN2) has been recently characterized as a prototypic immune mediator produced by various cell types being involved mainly in host defence. In addition, numerous studies have demonstrated its clinical value as a biomarker. This study aimed at defining the role of LCN2 in liver regeneration.

Methods

We studied LCN2 expression in wild-type mice in a model of partial hepatectomy (PH). Furthermore, we evaluated liver regeneration after PH in LCN-deficient mice compared to littermate controls. Serum levels of LCN2 were assessed in a small group of patients undergoing hepatic resection.

Results

LCN2 is dramatically induced in livers and sera of wild-type mice after PH, whereas liver LCN2-receptor expression was decreased. Sham operations did not affect hepatic and serum LCN2 expression. Although LCN2-deficient mice exhibited increased baseline liver expression indices, LCN2-deficient mice did not differ from wild-type mice with respect to hepatic proliferation suggesting that this molecule is not involved in hepatic repair. Only serum IL-1β levels were slightly lower in LCN−/− mice, whereas IL-6 serum levels did not differ between various tested animal groups. In humans undergoing hepatic resection, LCN2 levels increased significantly within 24 h following surgery.

Conclusions

LCN2, although massively induced in mice after PH, is not relevant in murine hepatic regeneration. Further, human studies have to define whether LCN2 could evolve as biomarker after liver surgery.

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