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肿瘤坏死因子在人微血管和大血管内皮细胞中诱导不同的基因表达程序。

TNF induces distinct gene expression programs in microvascular and macrovascular human endothelial cells.

作者信息

Viemann Dorothee, Goebeler Matthias, Schmid Sybille, Nordhues Ursula, Klimmek Kerstin, Sorg Clemens, Roth Johannes

机构信息

Department of Experimental Dermatology and Interdisciplinary Clinical Research Center, University of Münster, Röntgenstr. 21, 48149 Münster, Germany.

出版信息

J Leukoc Biol. 2006 Jul;80(1):174-85. doi: 10.1189/jlb.0905530. Epub 2006 Apr 14.

DOI:10.1189/jlb.0905530
PMID:16617158
Abstract

The relevance of the diversity of endothelial cells (ECs) for the response to inflammatory stimuli is currently not well defined. Using oligonucleotide microarray technique, we systematically analyzed the tumor necrosis factor (TNF)-induced expression profile in human microvascular ECs (HMEC) and macrovascular human umbilical vein ECs (HUVEC), analyzing 13,000 human genes by microarray analysis. Using strict inclusion and exclusion criteria, microarray analysis revealed that about half of the TNF-induced genes were specific for HMEC-1 or HUVEC. The microarray data could widely be confirmed by quantitative reverse transcriptase-polymerase chain reaction and at the protein level. It is interesting that the majority of those genes regulated depending on the cell type encoded for chemokines, cytokines, and cell surface molecules. Our results argue for a more careful consideration of specific effects restricted to distinct subtypes of ECs. The establishment of EC type-specific expression patterns may thus provide the basis for a selective manipulation of specific endothelial subtypes in different inflammatory diseases.

摘要

目前,内皮细胞(ECs)多样性与炎症刺激反应之间的相关性尚不明确。我们运用寡核苷酸微阵列技术,系统分析了肿瘤坏死因子(TNF)诱导的人微血管内皮细胞(HMEC)和人脐静脉大血管内皮细胞(HUVEC)中的基因表达谱,通过微阵列分析检测了13000个人类基因。采用严格的纳入和排除标准,微阵列分析显示,约一半的TNF诱导基因是HMEC-1或HUVEC特有的。微阵列数据在很大程度上可通过定量逆转录聚合酶链反应以及蛋白质水平得到证实。有趣的是,这些因细胞类型而受调控的基因大多编码趋化因子、细胞因子和细胞表面分子。我们的结果表明,需要更谨慎地考虑限于不同内皮细胞亚型的特定效应。因此,内皮细胞类型特异性表达模式的建立可能为在不同炎症性疾病中选择性操纵特定内皮细胞亚型提供基础。

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