The role of lipocalin-2 in liver regeneration

Liver Int. 2015 Apr;35(4):1195-202. doi: 10.1111/liv.12634. Epub 2014 Jul 25.

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.

Keywords: LCN2; biomarker; hepatic proliferation; lipocalin-2; liver regeneration; partial hepatectomy.

MeSH terms

  • Acute-Phase Proteins / deficiency
  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism*
  • Adult
  • Aged
  • Animals
  • Biomarkers / blood
  • Female
  • Hepatectomy / methods
  • Heterozygote
  • Homozygote
  • Humans
  • Interleukin-6 / blood
  • Lipocalin-2
  • Lipocalins / blood*
  • Lipocalins / genetics
  • Lipocalins / metabolism*
  • Liver / metabolism*
  • Liver / physiopathology
  • Liver / surgery
  • Liver Regeneration*
  • Male
  • Mice, Knockout
  • Middle Aged
  • Oncogene Proteins / deficiency
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Phenotype
  • Proto-Oncogene Proteins / blood*
  • Signal Transduction
  • Time Factors
  • Up-Regulation

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Interleukin-6
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • interleukin-6, mouse
  • Lcn2 protein, mouse