Table_2_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）通常定植于哺乳动物与鸟类的呼吸道，主要引发人类及动物的呼吸道疾病。截至目前，多杀性巴氏杆菌感染对宿主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，仍未得到充分阐释。本研究以新生猪气管上皮（newborn pig tracheal epithelial, NPTr）细胞作为体外模型，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（transepithelial electrical resistance, TEER）值，以及多种已知的细胞黏附连接相关分子的表达水平，研究发现多杀性巴氏杆菌感染会破坏NPTr细胞的屏障功能。通过RNA测序（RNA sequencing, RNA-Seq）分析，本研究鉴定出30个差异表达基因（differentially expressed genes, DEGs），其中包括编码血管内皮生长因子A（vascular endothelial growth factor A, VEGFA）的基因VEGFA，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（transforming growth factor-beta, TGF-β）信号通路（KEGG编号：ssc04350）、缺氧诱导因子1（hypoxia-inducible factor 1, HIF-1）信号通路（KEGG编号：ssc04066）、表皮生长因子受体（epidermal growth factor receptor, EGFR）酪氨酸激酶抑制剂耐药通路（KEGG编号：ssc01521）、肿瘤坏死因子（tumor necrosis factor, TNF）信号通路（KEGG编号：ssc04668）以及丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）信号通路（KEGG编号：ssc04010）；上述通路在其他组织与生物体中，已被证实参与炎性因子的产生调控以及上皮黏附与屏障功能的调节。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。