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在衣原体呼吸道感染中细胞焦亡相关基因的计算机识别和验证

In Silico Identification and Validation of Pyroptosis-Related Genes in Chlamydia Respiratory Infection.

机构信息

Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.

出版信息

Int J Mol Sci. 2023 Sep 1;24(17):13570. doi: 10.3390/ijms241713570.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b59/10488104/32b793465d5c/ijms-24-13570-g001.jpg

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