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Toxicogenomic study to identify potential signaling alterations related to nasal inflammatory damages induced by diesel exhaust particles in primary human nasal epithelial cells.
Toxicology in Vitro ( IF 3.2 ) Pub Date : 2020-09-04 , DOI: 10.1016/j.tiv.2020.104994
Hyun Soo Kim 1 , Hyo Jeong Kim 1 , Nahyun Kim 2 , Jae-Jun Song 3 , Bu-Soon Son 4 , Jun Hyuek Yang 1 , Cheol Min Lee 5 , Moo Kyun Park 2 , Young Rok Seo 1
Affiliation  

In this study, we aimed to identify signaling alteration caused by exposure to diesel exhaust particles (DEPs) using primary human nasal epithelial cells (PHNECs). Global gene expression profiles in PHNECs following 50 and 200 μg/ml of DEP exposure were identified using microarray analysis. To cover the limitation of array-based mRNA expression analysis, text-mining-based software was used to analyze the integrative biological networks and relevant disease-focused functions among identified DEP-responsive genes. The confidence was valued based on the connectivity between the analyzed pathway and marker candidates. Through a literature-based pathway analysis, the stimulation of inflammation- and immune response-related processes mediated by TNF were predicted as major signaling alterations in PHNECs caused by DEP exposure. CSF3, CXCL8, MMP1, and VEGFA were identified as key hub genes in the predicted pathway. Significant expression level changes in the five key genes following DEP exposure were validated in terms of protein and mRNA expression. Although further studies are required, our toxicogenomic investigation provides key clues to the exact mechanism underlying DEP-induced nasal inflammatory damage. It also suggests an efficient approach for other research on adverse effects occurring in the upper respiratory tract following DEP exposure.



中文翻译:

毒性基因组学研究,以确定与柴油机尾气颗粒在原代人鼻上皮细胞中引起的鼻炎损伤相关的潜在信号改变。

在这项研究中,我们旨在使用原代人鼻上皮细胞 (PHNEC) 来确定因接触柴油机尾气颗粒 (DEP) 引起的信号改变。使用微阵列分析确定暴露于 50 和 200 μg/ml DEP 后 PHNEC 中的全局基因表达谱。为了弥补基于阵列的 mRNA 表达分析的局限性,使用基于文本挖掘的软件来分析已识别的 DEP 响应基因之间的综合生物网络和相关的疾病聚焦功能。置信度是基于分析的通路和候选标记物之间的连通性来评估的。通过基于文献的通路分析,由 TNF 介导的炎症和免疫反应相关过程的刺激被预测为 DEP 暴露引起的 PHNEC 的主要信号改变。CSF3CXCL8MMP1VEGFA被鉴定为预测途径中的关键枢纽基因。在蛋白质和 mRNA 表达方面验证了 DEP 暴露后五个关键基因的显着表达水平变化。尽管需要进一步研究,但我们的毒理学研究为 DEP 诱导的鼻腔炎症损伤的确切机制提供了关键线索。它还为其他关于 DEP 暴露后上呼吸道不良反应的研究提出了一种有效的方法。

更新日期:2020-09-29
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