Whole transcriptome profiling of cardiac injury: insights from a neonatal mouse sepsis model.

Abstract

Background: Neonatal sepsis is characterized by an excessive immune response, often leading to multiple organ failure, including cardiac injury, and is a major cause of morbidity and mortality in newborns. Understanding the molecular mechanisms of sepsis-induced cardiac injury is crucial for developing therapeutic strategies.

Objective: To investigate transcriptomic changes and identify potential altered genes associated with cardiac injury in a neonatal sepsis model.

Methods: A neonatal sepsis model was established by cecal slurry injection. RNA sequencing analysis was performed on cardiac tissues from sepsis and control groups, followed by functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Interaction networks among mRNA, lncRNA, circRNA, and miRNA were constructed, and key regulatory genes were identified through protein-protein interaction (PPI) analysis.

Results: A total of 1537 differentially expressed mRNAs, 287 lncRNAs, and 730 circRNAs were identified. Functional analysis revealed significant involvement in immune response and inflammatory regulation. PPI network analysis identified six key genes-Ccl5, Il-6, Pole, Mcm2, Mcm5, Mcm10-that were significantly expressed in sepsis-induced cardiac tissue. Additionally, lncRNAs and circRNAs were found to participate in myocardial injury by regulating immune and inflammatory pathways.

Conclusions: This study identified six key genes involved in immune and inflammatory responses, playing critical roles in sepsis-induced cardiac injury in neonates. These findings provide new insights into the pathogenesis of sepsis-induced cardiac injury and offer potential therapeutic targets.