Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Int J Mol Sci. 2023 Sep 1;24(17):13570. doi: 10.3390/ijms241713570.
The incidence of respiratory infection is increasing, and its pathogenesis is still unclear. Pyroptosis, as a mode of inflammatory cell death, plays a vital role in the occurrence and development of respiratory infection. In this study, the potential pyroptosis-related genes involved in respiratory infection were identified by constructing a mouse model of infection combined with bioinformatics analysis. Through in-depth analysis of the RNA sequencing data, 13 differentially expressed pyroptosis-related genes were screened, including 1 downregulated gene and 12 upregulated genes. Gene ontology (GO) analysis showed that these genes mainly regulate inflammatory responses and produce IL-1β. Protein-protein interaction network analysis identified eight hub genes of interest: , , , , , , and . Through quantitative real-time PCR (qPCR) analysis, we found that the expression of these genes in the lungs of -infected mice was significantly reduced, consistent with the bioinformatics results. At the same time, we detected elevated levels of caspase-3, gasdermin D and gasdermin E proteins in the lungs of -infected mice, demonstrating that infection does induce pyroptosis. We then predicted nine miRNAs targeting these hub genes and constructed a key competitive endogenous RNA (ceRNA) network. In summary, we identified six key pyroptosis-related genes involved in respiratory infection and constructed a ceRNA network associated with these genes. These findings will improve understanding of the molecular mechanisms underlying pyroptosis in respiratory infections.
呼吸道感染的发病率正在上升,但其发病机制尚不清楚。细胞焦亡作为一种炎症细胞死亡方式,在呼吸道感染的发生和发展中起着至关重要的作用。本研究通过构建感染小鼠模型结合生物信息学分析,鉴定了与呼吸道感染相关的潜在焦亡相关基因。通过对 RNA 测序数据的深入分析,筛选出 13 个差异表达的焦亡相关基因,包括 1 个下调基因和 12 个上调基因。基因本体(GO)分析表明,这些基因主要调节炎症反应并产生 IL-1β。蛋白质-蛋白质相互作用网络分析确定了 8 个感兴趣的关键基因: 、 、 、 、 、 、 。通过定量实时 PCR(qPCR)分析,我们发现感染小鼠肺部这些基因的表达明显降低,与生物信息学结果一致。同时,我们在感染小鼠的肺部检测到 caspase-3、gasdermin D 和 gasdermin E 蛋白水平升高,表明 感染确实诱导了细胞焦亡。然后,我们预测了这些关键基因的 9 个靶向 miRNA,并构建了一个关键竞争性内源性 RNA(ceRNA)网络。总之,我们鉴定了参与呼吸道感染的 6 个关键焦亡相关基因,并构建了与这些基因相关的 ceRNA 网络。这些发现将有助于深入了解呼吸道感染中细胞焦亡的分子机制。