Transcriptomic study of lipopolysaccharide-induced sepsis damage in a mouse heart model.

Abstract

Sepsis is an emergency systemic illness caused by pathogen infection and the combined result of the underactivity and overactivity of a patient's own immune system. However, the molecular mechanism of this illness remains largely unknown. Lipopolysaccharide (LPS) was injected to establish a sepsis model, and heart tissue was used to analyze transcriptome changes in mice. LPS injection was used to develop a sepsis model, which resulted in cardiac tissue rearrangement and inflammatory response activation. An RNA-sequencing-based transcriptome assay using mouse heart tissue with or without LPS injection showed that 3,326 and 1,769 genes were upregulated and downregulated, respectively (>2-fold changes; P<0.05). Furthermore, these differentially expressed genes were classified into 20 pathways, including ‘Wnt signaling pathway’, ‘VEGF signaling pathway’ and ‘TGF-β signaling pathway’, and these altered genes were enriched in 41 Gene Ontology terms. The application of Wnt3a inhibited the activation of the LPS-induced inflammatory response and activated Wnt signaling, as well as protecting against LPS-mediated cardiac tissue damage in mice. In contrast, inhibition of Wnt signaling by injection of its inhibitor IWR induced plasminogen activator inhibitor-1 expression and resulted in cardiac structure derangement, which was similar to the symptoms caused by injection of LPS, suggesting that LPS-induced damage to heart tissue may be via inhibition of Wnt signaling. The present analyses showed that Wnt signaling serves a pivotal role in sepsis development and may improve our understanding of the molecular basis underlying sepsis.