Analysis of gene expression changes to elucidate the mechanism of chilling injury in precision-cut liver slices

Na Guan, Gregory M. Fahy, Geny M. M. Groothuis, Inge A. M. de Graaf*, Sylvia Blomsma

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)

Abstract

The exact mechanism of chilling injury (by a decrease of temperature to sub-physiological values), especially in the intact organ, is yet unknown. Precision-cut liver slices (PCLS), which closely resemble the organ from which they are derived, are an ideal in vitro model to study the mechanism of chilling injury in the intact organ.

In the present study we were able to separate chilling injury from other damaging events such as cryoprotectant toxicity and ice-crystal injury and performed micro-array analysis of regulated genes. Pathway analysis revealed that different stress responses, lipid/fatty acid and cholesterol biosynthesis and metabolism were affected by chilling. This indicates that the cell-membrane might be the primary site and sensor for chilling, which may initiate and amplify downstream intracellular signaling events. Most importantly, we were able to identify gene expression responses from stellate cells and Kupffer cells suggesting the involvement of all liver cell types in the injury. In conclusion, a broad spectrum of previously unknown gene expression changes induced by chilling was identified in the tissue. This is the first report of a systematic investigation on the mechanism of chilling injury in integrated tissue by micro-array analysis under conditions in which other sources of injury are minimal. (C) 2012 Elsevier Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)890-899
Number of pages10
JournalToxicology in Vitro
Volume27
Issue number2
DOIs
Publication statusPublished - Mar-2013

Keywords

  • Micro-array analysis
  • Chilling injury
  • Cryoprotectants
  • Cryoprotectant toxicity
  • Tissue banking
  • Cryopreservation
  • BILIARY CHOLESTEROL SECRETION
  • STELLATE CELL ACTIVATION
  • LIPID PHASE-TRANSITION
  • HEAT-SHOCK PROTEINS
  • DRUG-METABOLISM
  • MEMBRANE CHOLESTEROL
  • KIDNEY SLICES
  • BOAR SEMEN
  • RAT-LIVER
  • CRYOPRESERVATION

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