Use of gene expression profiles in cells of peripheral blood to identify new molecular markers of acute pancreatitis
Use of gene expression profiles in cells of peripheral blood to identify new molecular markers of acute pancreatitis
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DOI：
10.1001/archsurg.2007.73
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发表时间：
2008-03-01
影响因子：
--
通讯作者：
Zenilman, Michael
中科院分区：
文献类型：
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作者：
Bluth, Martin;Lin, Yin-yao;Zenilman, Michael
假设：血液白细胞在急性胰腺炎时介导局部和全身炎症中起主要作用。我们假设，外周血单核细胞（PBMC）在循环中表现出独特的基因表达的变化，可以提供一个“报告”。设计：为了确定急性胰腺炎期间血液白细胞的特定变化，我们研究了实验性胰腺炎大鼠模型（牛磺胆酸钠）中PBMC的基因转录谱。以正常大鼠、生理盐水对照和感染性休克模型作为对照。从各组（每组n=3）的PBMC中获得的互补RNA被应用于Affyphidine大鼠基因组DNA GeneChip arrays.Main Outcome Measure：Changes in gene expression.Results：从分析的8799个大鼠基因中，有140个基因在胰腺炎急性期的PBMC中的表达显示出独特的显著变化，但在脓毒症中没有。在140个基因中，57个基因表达上调，69个基因表达下调。血小板衍生生长因子受体、前列腺素E-2受体和磷脂酶D是最高上调基因。其他包括参与G蛋白偶联受体和转化生长因子β介导的信号通路的基因，而与细胞凋亡、糖皮质激素受体甚至胆囊收缩素受体相关的基因则下调。结论：PBMCs转录谱的微阵列分析表明，与分子和胰腺功能独特相关的基因在急性胰腺炎中表现出差异表达。在重症胰腺炎期间从容易获得的来源获得的基因分析可以确定疾病严重程度的替代标志物。
Hypothesis: Blood leukocytes play a major role in mediating local and systemic inflammation during acute pancreatitis. We hypothesize that peripheral blood mononuclear cells (PBMCs) in circulation exhibit unique changes in gene expression and could provide a "reporter". function that reflects the inflammatory response in the pancreas with acute pancreatitis.Design: To determine specific changes in blood leukocytes during acute pancreatitis, we studied the gene transcription profile in PBMCs in a rat model of experimental pancreatitis (sodium taurocholate). Normal rats, saline controls, and a model of septic shock were used as a controls. Complementary RNA obtained from PBMCs of each group (n=3 in each group) were applied to Affymetrix rat genome DNA GeneChip arrays.Main Outcome Measure: Changes in gene expression.Results: From the 8799 rat genes analyzed, 140 genes showed unique significant changes in their expression in PBMCs during the acute phase of pancreatitis, but not in sepsis. Among the 140 genes, 57 were up-regulated, while 69 were down-regulated. Platelet-derived growth factor receptor, prostaglandin E-2 receptor, and phospholipase D, were among the top up-regulated genes. Others included genes involved in G protein-coupled receptor and transforming growth factor beta-mediated signaling pathways, while genes associated with apoptosis, glucocorticoid receptors, and even the cholecystokinin receptor were down-regulated.Conclusions: Microarray analysis in transcriptional profiling of PBMCs showed that genes that are uniquely related to molecular and pancreatic function display differential expression in acute pancreatitis. Profiling genes obtained from an easily accessible source during severe pancreatitis may identify surrogate markers for disease severity.