Transcriptomic analysis of peritoneal cells in a mouse model of sepsis: confirmatory and novel results in early and late sepsis

Abstract

BackgroundThe events leading to sepsis start with an invasive infection of a primary organ of the body followed by an overwhelming systemic response. Intra-abdominal infections are the second most common cause of sepsis. Peritoneal fluid is the primary site of infection in these cases. A microarray-based approach was used to study the temporal changes in cells from the peritoneal cavity of septic mice and to identify potential biomarkers and therapeutic targets for this subset of sepsis patients.ResultsWe conducted microarray analysis of the peritoneal cells of mice infected with a non-pathogenic strain of Escherichia coli. Differentially expressed genes were identified at two early (1 h, 2 h) and one late time point (18 h). A multiplexed bead array analysis was used to confirm protein expression for several cytokines which showed differential expression at different time points based on the microarray data. Gene Ontology based hypothesis testing identified a positive bias of differentially expressed genes associated with cellular development and cell death at 2 h and 18 h respectively. Most differentially expressed genes common to all 3 time points had an immune response related function, consistent with the observation that a few bacteria are still present at 18 h.ConclusionsTranscriptional regulators like PLAGL2, EBF1, TCF7, KLF10 and SBNO2, previously not described in sepsis, are differentially expressed at early and late time points. Expression pattern for key biomarkers in this study is similar to that reported in human sepsis, indicating the suitability of this model for future studies of sepsis, and the observed differences in gene expression suggest species differences or differences in the response of blood leukocytes and peritoneal leukocytes.

MicroRNA-598 inhibition ameliorates LPS-induced acute lung injury in mice through upregulating Ebf1 expression

“…Previous study has demonstrated that Ebf1 expression was significantly upregulated in the early stages of sepsis (Bhatty et al. 2012 ). Intriguingly, Ebf1 mRNA was reported to be regulated by multiple altered miRNAs in a rat model of ARDS (Huang et al.…”

MicroRNA-598 inhibition ameliorates LPS-induced acute lung injury in mice through upregulating Ebf1 expression

“…Ebf1 is a transcription factor, which is important for early B cell development (Gao et al 2009). Previous study has demonstrated that Ebf1 expression was signi cantly upregulated in the early stages of sepsis (Bhatty et al 2012). Intriguingly, Ebf1 mRNA was reported to be regulated by multiple altered miRNAs in a rat model of ARDS (Huang et al 2014).…”

A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation

“…Ebf1 is reported to be expressed in several CNS regions and has been implicated in CNS function and development [ 102 – 105 ]. This factor has also been implicated in B-cell development and peripheral inflammation [ 106 – 108 ]. Furthermore, Ebf1 may exert a role in the pathophysiology of multiple sclerosis [ 109 ].…”