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

Mohan Krishnan, Kopperuncholan Namachivayam, Feng Cheng, Rays H.Y. Jiang, Jaime Flores-Torres, Benjamin A. Torres, Akhil Maheshwari

Research output: Contribution to journalArticle

Abstract

Background: We have shown previously that enteral administration of 2, 4, 6-trinitrobenzene sulfonic acid in 10-d-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 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-mediated intestinal injury could be used as a NEC model, we compared gene expression profiles of TNBS-mediated intestinal injury and NEC. Methods: Whole-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. Results: We 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 4,440 differentially-expressed genes (DEGs) in murine TNBS-mediated injury and 1,377 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. Conclusion: Murine neonatal TNBS-mediated enterocolitis and human NEC activate nearly-identical biological processes, signaling pathways, and transcriptional networks.

Original languageEnglish (US)
Pages (from-to)99-112
Number of pages14
JournalPediatric Research
Volume81
Issue number1
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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