PMID- 23111282 OWN - NLM STAT- MEDLINE DCOM- 20130820 LR - 20141120 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 27 IP - 2 DP - 2013 Mar TI - Analysis of gene expression changes to elucidate the mechanism of chilling injury in precision-cut liver slices. PG - 890-9 LID - S0887-2333(12)00285-8 [pii] LID - 10.1016/j.tiv.2012.10.009 [doi] AB - 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. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Guan, Na AU - Guan N AD - Division of Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen, The Netherlands. FAU - Blomsma, Sylvia A AU - Blomsma SA FAU - Fahy, Gregory M AU - Fahy GM FAU - Groothuis, Geny M M AU - Groothuis GM FAU - de Graaf, Inge A M AU - de Graaf IA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121027 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Cryoprotective Agents) RN - 63231-63-0 (RNA) RN - 8L70Q75FXE (Adenosine Triphosphate) SB - IM MH - Adenosine Triphosphate/metabolism MH - Animals MH - Cell Survival/drug effects MH - Cold Temperature/*adverse effects MH - Cryoprotective Agents/*adverse effects MH - Gene Expression Profiling MH - In Vitro Techniques MH - Liver/*injuries/*metabolism MH - Male MH - Oligonucleotide Array Sequence Analysis MH - Organ Preservation MH - RNA/genetics MH - Rats MH - Rats, Wistar EDAT- 2012/11/01 06:00 MHDA- 2013/08/21 06:00 CRDT- 2012/11/01 06:00 PHST- 2012/06/14 00:00 [received] PHST- 2012/10/10 00:00 [revised] PHST- 2012/10/11 00:00 [accepted] PHST- 2012/11/01 06:00 [entrez] PHST- 2012/11/01 06:00 [pubmed] PHST- 2013/08/21 06:00 [medline] AID - S0887-2333(12)00285-8 [pii] AID - 10.1016/j.tiv.2012.10.009 [doi] PST - ppublish SO - Toxicol In Vitro. 2013 Mar;27(2):890-9. doi: 10.1016/j.tiv.2012.10.009. Epub 2012 Oct 27.