Table_1_Transcriptome Differences in Pig Tracheal Epithelial Cells in Response to Pasteurella Multocida Infection.XLSX

Pasteurella multocida generally colonizes mammalian/bird respiratory tracts and mainly causes respiratory disorders in both humans and animals. To date, the effects of P. multocida infection on the respiratory epithelial barriers and molecules in host respiratory epithelial cells in their response to P. multocida infection are still not well-known. In this study, we used newborn pig tracheal epithelial (NPTr) cells as an in vitro model to investigate the effect of P. multocida infection on host respiratory epithelial barriers. By detecting the transepithelial electrical resistance (TEER) values of NPTr cells and the expression of several known molecules associated with cell adherens and junctions, we found that P. multocida infection disrupted the barrier functions of NPTr cells. By performing RNA sequencing (RNA-Seq), we determined 30 differentially expressed genes (DEGs), including the vascular endothelial growth factor A (VEGFA) encoding gene VEGFA, which participated in biological processes (GO:0034330, GO:0045216, and GO:0098609) closely related to epithelial adhesion and barrier functions. These 30 DEGs participated in 22 significant signaling pathways with a p-value < 0.05, including the transforming growth factor (TGF)-beta signaling pathway (KEGG ID: ssc04350), hypoxia-inducible factor 1 (HIF-1) signaling pathway (KEGG ID: ssc04066), epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance (KEGG ID: ssc01521), tumor necrosis factor (TNF) signaling pathway (KEGG ID: ssc04668), and mitogen-activated protein kinase (MAPK) signaling pathway (KEGG ID: ssc04010), which are reported to have roles in contributing to the production of inflammatory factors as well as the regulation of epithelial adhesion and barrier function in other tissues and organisms. The results presented in this study may help improve our understanding of the pathogenesis of P. multocida.

多杀性巴氏杆菌（Pasteurella multocida）通常定殖于哺乳动物和鸟类的呼吸道，主要引发人类与动物的呼吸道疾病。截至目前，多杀性巴氏杆菌感染对呼吸道上皮屏障的影响，以及宿主呼吸道上皮细胞针对该菌感染的应答分子机制仍不甚明确。本研究以新生猪气管上皮（NPTr）细胞为体外模型，探究多杀性巴氏杆菌感染对宿主呼吸道上皮屏障的作用。通过检测NPTr细胞的跨上皮电阻（TEER）值，以及多种已知的细胞黏附连接相关分子的表达情况，我们发现多杀性巴氏杆菌感染会破坏NPTr细胞的屏障功能。借助RNA测序（RNA-Seq）分析，我们筛选得到30个差异表达基因（DEGs），其中包括编码血管内皮生长因子A（VEGFA）的VEGFA基因，该基因参与了与上皮黏附及屏障功能密切相关的生物学过程（GO:0034330、GO:0045216及GO:0098609）。这30个差异表达基因参与了22个p值<0.05的显著富集信号通路，包括转化生长因子β（TGF-β）信号通路（KEGG ID: ssc04350）、缺氧诱导因子1（HIF-1）信号通路（KEGG ID: ssc04066）、表皮生长因子受体（EGFR）酪氨酸激酶抑制剂耐药通路（KEGG ID: ssc01521）、肿瘤坏死因子（TNF）信号通路（KEGG ID: ssc04668）以及丝裂原活化蛋白激酶（MAPK）信号通路（KEGG ID: ssc04010）；上述通路已被证实可参与其他组织与生物体的炎症因子产生过程，并调控上皮黏附与屏障功能。本研究结果有助于加深我们对多杀性巴氏杆菌致病机制的理解。