title: Trinitrobenzene sulfonic acid-induced intestinal injury in neonatal mice activates transcriptional networks similar to those seen in human necrotizing enterocolitis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Murine neonatal TNBS-mediated enterocolitis and human NEC activate nearly-identical biological processes, signaling pathways, and transcriptional networks.
authors.affiliation: Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Krishnan
authors.initials: K
authors.lastname: MohanKumar
authors.affiliation: Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Kopperuncholan
authors.initials: K
authors.lastname: Namachivayam
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, Florida.|Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, Florida.
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
authors.affiliation: Department of Global Health, College of Public Health, University of South Florida, Tampa, Florida.
authors.forename: Rays H Y
authors.initials: RH
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Jaime
authors.initials: J
authors.lastname: Flores-Torres
authors.affiliation: Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Torres
authors.affiliation: Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.|Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida.|Department of Community and Family Health, College of Public Health, University of South Florida, Tampa, Florida.
authors.forename: Akhil
authors.initials: A
authors.lastname: Maheshwari
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000209:etiology / Q000235:genetics*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000293:injuries*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity*
chemical_list: D008070:Lipopolysaccharides; D014302:Trinitrobenzenesulfonic Acid