Abstract
Sepsis is a life-threatening disease induced by a systemic inflammatory response, which leads to organ dysfunction and mortality. In sepsis, the host immune response is depressed and unable to cope with infection; no drug is currently available to treat this. The lungs are frequently the starting point for sepsis. This study aimed to identify potential genes for diagnostics and therapeutic purposes in sepsis by a comprehensive bioinformatics analysis. Our criteria are to unravel sepsis-associated signature genes from gene expression datasets. Differentially expressed genes (DEGs) were identified from samples of sepsis patients using a meta-analysis and then further subjected to functional enrichment and protein‒protein interaction (PPI) network analysis for examining their potential functions. Finally, the expression of the topmost upregulated genes (ARG1, IL1R2, ELANE, MMP9) was quantified by reverse transcriptase-PCR (RT-PCR), and myeloperoxidase (MPO) expression was confirmed by immunohistochemistry (IHC) staining in the lungs of a well-established sepsis mouse model. We found that all the four genes were upregulated in semiquantitative RT-PCR studies; however, MMP9 showed a nonsignificant increase in expression. MPO staining showed strong immunoreactivity in sepsis as compared to the control. This study demonstrates the role of significant and widespread immune activation (IL1R2, MMP9), along with oxidative stress (ARG1) and the recruitment of neutrophils, in sepsis (ELANE, MPO).
Highlights
Sepsis is a clinically heterogeneous and biologically complex disease characterized by the improper response of the immune system due to an infection caused by bacteria, viruses, fungi, or parasites, Genes 2019, 10, 1005; doi:10.3390/genes10121005 www.mdpi.com/journal/genesGenes 2019, 10, 1005 leading to organ dysfunction [1]
differentially expressed genes (DEGs), normalized expression data were obtained from Gene Expression Omnibus (GEO) and an analysis was done based on two criteria, fold change (FC) and p-vaule (Figure 1)
The lung is one of the organs most often affected in sepsis, mainly because lung lung infection/pneumonia is often the initial point of the septic process and almost all infections infection/pneumonia is often the initial point of the septic process and almost all infections are are associated with a systemic inflammatory response (SIRS) in which the lung is the first affected associated with a systemic inflammatory response (SIRS) in which the lung is the first affected organ organ [33]
Summary
Sepsis is a clinically heterogeneous and biologically complex disease characterized by the improper response of the immune system due to an infection caused by bacteria, viruses, fungi, or parasites, Genes 2019, 10, 1005; doi:10.3390/genes10121005 www.mdpi.com/journal/genesGenes 2019, 10, 1005 leading to organ dysfunction [1]. Sepsis is a clinically heterogeneous and biologically complex disease characterized by the improper response of the immune system due to an infection caused by bacteria, viruses, fungi, or parasites, Genes 2019, 10, 1005; doi:10.3390/genes10121005 www.mdpi.com/journal/genes. Sepsis incidence rates have increased rapidly and the World Health Organization (WHO) has declared it as a key healthcare priority for the coming decade. The major cause of sepsis is a lack of knowledge about the pathophysiological and biochemical mechanisms behind the perturbation of the host immune response. This reflects the patient’s risk and often involves a delay in diagnosis. The pathogenesis of sepsis on a genetic basis is underappreciated, but death from this acute condition is more heritable than cancer [5]
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