Proteomic Profiling in Lipocalin 2 Deficient Mice Under Normal and Inflammatory Conditions

J Proteomics. 2013 Jan 14;78:188-96. doi: 10.1016/j.jprot.2012.11.021. Epub 2012 Dec 3.

Abstract

Lipocalin 2 (LCN2) belongs to the superfamily of lipocalins which represent a group of small secreted proteins classified as extracellular transport proteins expressed in many tissues. LCN2 is strongly increased in experimental models of acute and chronic liver injuries. To investigate the function of LCN2 in normal liver homeostasis and under conditions of inflammatory liver injury, we comparatively analyzed hepatic extracts taken from Lcn2-deficient and wild type mice under basal conditions and after stimulation with lipopolysaccharides. Liver was chemically and mechanically lysed and extracts were subjected to 2-D-DIGE after minimal labeling (G200 and G300 dyes) using an appropriate internal standard (G100). Afterwards MALDI TOF MS and MS/MS were used to identify differentially expressed proteins. Proteins that were identified to be differentially expressed include for example the chloride intracellular channel protein 4 (CLIC4), aminoacylase 1 and transketolase. The altered expression of respective genes was confirmed by Western blot analysis and further validated by quantitative real time PCR. Altogether, the complex expression alterations in mice lacking LCN2 under normal conditions and after exposure to inflammatory stimuli reveal that LCN2 has essential function in liver homeostasis and in the onset of inflammatory responses in which LCN2 expression dramatically increases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism*
  • Animals
  • Gene Expression Profiling*
  • Gene Expression Regulation*
  • Inflammation / chemically induced
  • Inflammation / genetics
  • Inflammation / metabolism
  • Lipocalin-2
  • Lipocalins / genetics
  • Lipocalins / metabolism*
  • Lipopolysaccharides / toxicity
  • Liver / metabolism*
  • Mice
  • Mice, Knockout
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Proteome / biosynthesis*
  • Proteome / genetics
  • Proteomics*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods

Substances

  • Acute-Phase Proteins
  • Lipocalin-2
  • Lipocalins
  • Lipopolysaccharides
  • Oncogene Proteins
  • Proteome
  • Lcn2 protein, mouse