Analysis of gene expression changes to elucidate the mechanism of chilling injury in precision-cut liver slices
Analysis of gene expression changes to elucidate the mechanism of chilling injury in precision-cut liver slices
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DOI：
10.1016/j.tiv.2012.10.009
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发表时间：
2013-03-01
影响因子：
3.2
通讯作者：
de Graaf, Inge A. M.
中科院分区：
文献类型：
--
作者：
Guan, Na;Blomsma, Sylvia A.;de Graaf, Inge A. M.
冷害的确切机制（通过温度降低到亚生理值），特别是在完整的器官，还不清楚。精密切取的肝脏切片（PCLS）是研究完整器官冷损伤机制的理想离体模型，本研究将冷损伤与其他损伤事件（如冷冻保护剂毒性和冰晶损伤）区分开来，并进行了调控基因的微阵列分析。途径分析表明，低温对不同的胁迫反应、脂类/脂肪酸和胆固醇的生物合成和代谢均有影响。这表明，细胞膜可能是主要的网站和传感器的冷却，这可能会启动和放大下游的细胞内信号事件。最重要的是，我们能够鉴定来自星状细胞和枯否细胞的基因表达反应，表明所有肝细胞类型都参与了损伤。总之，一个以前未知的基因表达变化诱导的组织中确定了一个广泛的。这是第一次报告的系统调查的机制，在完整的组织微阵列分析的条件下，在其他来源的伤害是最小的。(C)2012爱思唯尔有限公司保留所有权利。
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.