MohanKumar Krishnan, Namachivayam Kopperuncholan, Cheng Feng, Jiang Rays H Y, Flores-Torres Jaime, Torres Benjamin A, Maheshwari Akhil
Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.
Department of Pharmaceutical Science, College of Pharmacy, University of South Florida, Tampa, Florida.
Pediatr Res. 2017 Jan;81(1-1):99-112. doi: 10.1038/pr.2016.189. Epub 2016 Sep 22.
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.
我们之前已经表明，在10日龄的C57BL/6幼崽中肠内给予2,4,6-三硝基苯磺酸会导致急性坏死性小肠结肠炎，其组织病理学和炎症变化与人类坏死性小肠结肠炎（NEC）相似。为了确定小鼠新生儿2,4,6-三硝基苯磺酸（TNBS）介导的肠道损伤是否可作为NEC模型，我们比较了TNBS介导的肠道损伤和NEC的基因表达谱。
对对照组和经TNBS处理的幼崽（每组n = 8）的近端结肠进行全基因组微阵列分析。为了进行比较，我们从公共数据库下载了NEC（n = 5）和手术对照组（n = 4）的人类微阵列数据。使用Partek Genomics Suite和Ingenuity Pathway Analysis软件程序对数据进行分析。
我们在小鼠TNBS介导的肠道损伤和人类NEC中检测到基因表达的广泛变化。使用±1.5的倍数变化临界值，我们在小鼠TNBS介导的损伤中鉴定出4440个差异表达基因（DEG），在NEC中鉴定出1377个。小鼠TNBS介导的损伤和NEC在直系同源基因的表达上产生了相似的变化（r = 0.611，P < 0.
