Identification and validation of autophagy-related genes in exogenous sepsis-induced acute respiratory distress syndrome

Yongpeng Xie; Wenxia Hu; Xiaobin Chen; Panpan Ren; Chongchong Ye; Yanli Wang; Jiye Luo; Xiaomin Li

doi:10.1002/iid3.691

Identification and validation of autophagy-related genes in exogenous sepsis-induced acute respiratory distress syndrome

Immun Inflamm Dis. 2022 Oct;10(10):e691. doi: 10.1002/iid3.691.

Authors

Yongpeng Xie^{1

2}, Wenxia Hu^{1

2}, Xiaobin Chen^{1

2}, Panpan Ren¹, Chongchong Ye¹, Yanli Wang¹, Jiye Luo¹, Xiaomin Li^{1

2}

Affiliations

¹ Department of Emergency and Critical Care Medicine, Lianyungang Clinical College of Nanjing Medical University, The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.
² The Institute of Emergency Medicine of Lianyungang, Lianyungang, Jiangsu, China.

Abstract

Objective: To analyze the differential expression of autophagy-related genes of sepsis-induced acute respiratory distress syndrome (ARDS) as potential markers for early diagnosis.

Methods: Male Sprague-Dawley rats (aged 8 weeks) were selected and randomly divided into sepsis-induced ARDS group (n = 6) and a normal control group (n = 6). Lung tissue samples were collected for high-throughput sequencing using Illumina HiSeq sequencing platform in the paired-end sequencing mode. Differentially expressed genes (DEGs) were screened by DESeq. 2 software [|log2FC | ≥1 and p < .05] and autophagy-related genes were identified using Mouse Genome Informatics. Co-expressed autophagy-related DEGs from these two datasets were filtered by construction of a Venn diagram. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these autophagy-related DEGs and a protein interaction network was constructed using STRING and Cytoscape software to identify hub genes, which were verified by real-time quantitative polymerase chain reaction (qRT-PCR).

Results: A total of 42 autophagy-related DEGs (26 upregulated genes and 16 downregulated genes) were identified. The GO and KEGG pathway analyses showed enrichment in 969 biological processes (BPs), three cellular components (CCs), eight molecular functions (MFs) and 27 signaling pathways. The protein interaction (PPI) network revealed 42 node proteins and 75 interacting edges, with an average node degree of 3.52, and an average local clustering coefficient of 0.509. Among the top 10 hub genes with the RNA-Seq, six hub genes (Stat3, Il10, Ifng, Hmox1, Hif1a, and Nod2) were validated by qRT-PCR (all p < .05).

Conclusion: 42 potential autophagy-related genes associated with sepsis-induced ARDS lung injury were identified and six hub genes (Stat3, Il10, Ifng, Hmox1, Hif1a, and Nod2) may affect the development of ARDS by regulating autophagy. These results expanded our understanding of ARDS and might be useful in treatment of exogenous sepsis-induced ARDS.

Keywords: acute respiratory distress syndrome; autophagy; hub gene; sepsis; transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Autophagy / genetics
Gene Expression Profiling / methods
Interleukin-10 / genetics
Male
Rats
Rats, Sprague-Dawley
Respiratory Distress Syndrome* / etiology
Respiratory Distress Syndrome* / genetics
Sepsis* / complications
Sepsis* / genetics

Substances

Interleukin-10