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

Author:

Sun Ruoyuan1,Zheng Wenjing1,Yang Shuaini1,Zeng Jiajia1,Tuo Yuqing1,Tan Lu1,Zhang Hong1,Bai Hong1

Affiliation:

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

Abstract

The incidence of Chlamydia trachomatis 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 Chlamydia trachomatis respiratory infection. In this study, the potential pyroptosis-related genes involved in Chlamydia trachomatis respiratory infection were identified by constructing a mouse model of C. muridarum 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: Tnf, Tlr2, Il1b, Nlrp3, Tlr9, Mefv, Zbp1 and Tnfaip3. Through quantitative real-time PCR (qPCR) analysis, we found that the expression of these genes in the lungs of C. muridarum-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 C. muridarum-infected mice, demonstrating that Chlamydia trachomatis 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 Chlamydia trachomatis respiratory infection and constructed a ceRNA network associated with these genes. These findings will improve understanding of the molecular mechanisms underlying pyroptosis in Chlamydia trachomatis respiratory infections.

Funder

National Natural Science Foundation of China

Key Program of Tianjin Science and Technology Commission

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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