Miura Aya, Honma Reiko, Togashi Takushi, Yanagisawa Yuka, Ito Emi, Imai Jun-Ichi, Isogai Takao, Goshima Naoki, Watanabe Shinya, Nomura Nobuo
Graduate School of Life and Environmental Science, University of Tsukuba, 1-1-1 Ten-noudai, Tsukuba, Ibaraki 305-8572, Japan.
FEBS Lett. 2006 Dec 22;580(30):6871-9. doi: 10.1016/j.febslet.2006.11.041. Epub 2006 Nov 27.
Endothelial cells play an important role in terms of biological functions by responding to a variety of stimuli in the blood. However, little is known about the molecular mechanism involved in rendering the variety in the cellular response. To investigate the variety of the cellular responses against exogenous stimuli at the gene expression level, we attempted to describe the cellular responses with comprehensive gene expression profiles, dissect them into multiple response patterns, and characterize the response patterns according to the information accumulated so far on the genes included in the patterns. We comparatively analyzed in parallel the gene expression profiles obtained with DNA microarrays from normal human coronary artery endothelial cells (HCAECs) stimulated with multiple cytokines, interleukin-1beta, tumor necrosis factor-alpha, interferon-beta, interferon-gamma, and oncostatin M, which are profoundly involved in various functional responses of endothelial cells. These analyses revealed that the cellular responses of HCAECs against these cytokines included at least 15 response patterns specific to a single cytokine or common to multiple cytokines. Moreover, we statistically extracted genes contained within the individual response patterns and characterized the response patterns with the genes referring to the previously accumulated findings including the biological process defined by the Gene Ontology Consortium (GO). Out of the 15 response patterns in which at least one gene was successfully extracted through the statistical approach, 11 response patterns were differentially characterized by representing the number of genes contained in individual criteria of the biological process in the GO only. The approach to dissect cellular responses into response patterns and to characterize the pattern at the gene expression level may contribute to the gaining of insight for untangling the diversity of cellular functions.
内皮细胞通过对血液中的多种刺激做出反应，在生物学功能方面发挥着重要作用。然而，对于导致细胞反应多样性的分子机制却知之甚少。为了在基因表达水平上研究针对外源性刺激的细胞反应多样性，我们试图用全面的基因表达谱来描述细胞反应，将它们分解为多种反应模式，并根据目前积累的有关这些模式中所含基因的信息来表征这些反应模式。我们同时比较分析了用DNA微阵列从正常人冠状动脉内皮细胞（HCAECs）获得的基因表达谱，这些细胞受到多种细胞因子的刺激，包括白细胞介素-1β、肿瘤坏死因子-α、干扰素-β、干扰素-γ和制瘤素M，它们都深度参与内皮细胞的各种功能反应。这些分析表明，HCAECs对这些细胞因子的细胞反应包括至少15种特定于单一细胞因子或多种细胞因子共有的反应模式。此外，我们通过统计学方法提取了各个反应模式中包含的基因，并根据先前积累的发现，包括基因本体联合会（GO）定义的生物学过程，用这些基因来表征反应模式。在通过统计学方法成功提取至少一个基因得到的15种反应模式中，有11种反应模式仅通过在GO生物学过程的各个标准中所含基因的数量来进行差异表征。将细胞反应分解为反应模式并在基因表达水平上表征这些模式的方法，可能有助于深入了解细胞功能的多样性。
