Trinitrobenzene sulfonic acid-induced intestinal injury in neonatal mice activates transcriptional networks similar to those seen in human necrotizing enterocolitis.

Abstract

BackgroundWe have shown previously that enteral administration of 2, 4, 6-trinitrobenzene sulfonic acid in 10-day-old C57BL/6 pups produces an acute necrotizing enterocolitis with histopathological and inflammatory changes similar to human necrotizing enterocolitis (NEC). To determine whether murine neonatal TNBS-mediated intestinal injury could be used as a NEC model, we compared gene expression profiles of TNBS-mediated intestinal injury and NEC.MethodsWhole genome microarray analysis was performed on proximal colon from control and TNBS-treated pups (n=8/group). For comparison, we downloaded human microarray data of NEC (n=5) and surgical control (n=4) from a public database. Data were analyzed using the software programs Partek Genomics Suite and Ingenuity Pathway Analysis.ResultsWe detected extensive changes in gene expression in murine TNBS-mediated intestinal injury and human NEC. Using fold-change cut-offs of ±1.5, we identified 4440 differentially-expressed genes (DEGs) in murine TNBS-mediated injury and 1377 in NEC. Murine TNBS-mediated injury and NEC produced similar changes in expression of orthologous genes (r = 0.611, p<0.001), and also activated nearly-identical biological processes and pathways. Lipopolysaccharide was top predicted upstream regulator in both the murine and human datasets.ConclusionsMurine neonatal TNBS-mediated enterocolitis and human NEC activate nearly-identical biological processes, signaling pathways, and transcriptional networks.