Pulmonary microvascular endothelium barrier plays a critical role in protecting the pulmonary tissue from inflammatory injury in acute respiratory distress syndrome and acute lung injury (ARDS/ALI). The dysregulation of IQ-GTPase-activating protein 1 (IQGAP1) was an important etiology of endothelium barrier injury. However, significant differentially expressed genes (DEGs) and signaling pathways directly regulated by IQGAP1 are too complicated to fully understand. In this research, we identified a total of 1216 DEGs regulated by knockdown of IQGAP1 in rat pulmonary microvascular endothelial cells on the basis of transcriptomic RNA sequencing (RNA-Seq). Among them, 665 were upregulated DEGs and 551 were downregulated DEGs. Gene ontology analysis has revealed that upregulated DEGs were mainly enriched in DNA replication, cell cycle, and chromosome formation, while downregulated DEGs were mainly involved in the regulation of many cellular bioprocesses including cell proliferation, cell adhesion, and cell migration. Kyoto Encyclopedia of Genes and Genomes pathways analysis toward DEGs showed that upregulated pathways were mainly about DNA replication, while the significantly downregulated pathways were about TNF signaling pathway and some inflammatory- and proliferation-related pathways. Furthermore, we choose 30 DEGs for validation by qRT-PCR, the results were quite consistent with the RNA-Seq. In addition, we also found that knockdown of IQGAP1 caused a significant impact on many cytokines and inflammatory factors, which play a vital role in ARDS/ALI. In summary, in this study on the basis of RNA-Seq, we found IQGAP1 not only exerts a crucial role in microvascular endothelium barrier but also plays an important role in inflammation, which might provide a new insight for future study on IQGAP1 in the related diseases such as ARDS/ALI.

中文翻译：

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IQGAP1基因敲除对肺微血管内皮细胞的转录组学分析。

肺微血管内皮屏障在保护肺组织免受急性呼吸窘迫综合征和急性肺损伤（ARDS / ALI）的炎症损伤中起关键作用。IQ-GTPase激活蛋白1（IQGAP1）的失调是内皮屏障损伤的重要病因。但是，直接由IQGAP1调控的显着差异表达基因（DEG）和信号传导途径过于复杂，无法完全理解。在这项研究中，我们根据转录组RNA测序（RNA-Seq）在大鼠肺微血管内皮细胞中共鉴定了1216个受IQGAP1敲低调节的DEG。其中，665个上调的DEG和551个下调的DEG。基因本体论分析显示，上调的DEG主要富集于DNA复制，细胞周期，和染色体形成，而下调的DEGs主要参与许多细胞生物过程的调控，包括细胞增殖，细胞粘附和细胞迁移。京都基因和基因组百科全书对DEGs的通路分析表明，上调的通路主要与DNA复制有关，而显着下调的通路与TNF信号通路以及某些与炎症和增殖相关的通路有关。此外，我们选择了30个DEG进行qRT-PCR验证，结果与RNA-Seq相当一致。此外，我们还发现敲低IQGAP1对许多细胞因子和炎性因子产生了重大影响，而这些因子在ARDS / ALI中起着至关重要的作用。总之，在这项基于RNA-Seq的研究中，