title: Relevance of TNBS-colitis in rats: a methodological study with endoscopic, histologic and Transcriptomic [corrected] characterization and correlation to IBD.
abstract: BACKGROUND
  Rectal instillation of trinitrobenzene sulphonic acid (TNBS) in ethanol is an established model for inflammatory bowel disease (IBD). We aimed to 1) set up a TNBS-colitis protocol resulting in an endoscopic and histologic picture resembling IBD, 2) study the correlation between endoscopic, histologic and gene expression alterations at different time points after colitis induction, and 3) compare rat and human IBD mucosal transcriptomic data to evaluate whether TNBS-colitis is an appropriate model of IBD.
  
  
  RESULTS
  Five female Sprague Daley rats received TNBS diluted in 50% ethanol (18 mg/0.6 ml) rectally. The rats underwent colonoscopy with biopsy at different time points. RNA was extracted from rat biopsies and microarray was performed. PCR and in situ hybridization (ISH) were done for validation of microarray results. Rat microarray profiles were compared to human IBD expression profiles (25 ulcerative colitis Endoscopic score demonstrated mild to moderate colitis after three and seven days, but declined after twelve days. Histologic changes corresponded with the endoscopic appearance. Over-represented Gene Ontology Biological Processes included: Cell Adhesion, Immune Response, Lipid Metabolic Process, and Tissue Regeneration. IL-1α, IL-1β, TLR2, TLR4, PRNP were all significantly up-regulated, while PPARγ was significantly down-regulated. Among genes with highest fold change (FC) were SPINK4, LBP, ADA, RETNLB and IL-1α. The highest concordance in differential expression between TNBS and IBD transcriptomes was three days after colitis induction. ISH and PCR results corresponded with the microarray data. The most concordantly expressed biologically relevant pathways included TNF signaling, Cell junction organization, and Interleukin-1 processing.
  
  
  CONCLUSIONS
  Endoscopy with biopsies in TNBS-colitis is useful to follow temporal changes of inflammation visually and histologically, and to acquire tissue for gene expression analyses. TNBS-colitis is an appropriate model to study specific biological processes in IBD.
authors: Department of Gastroenterology and Hepatology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. Oystein.Brenna@stolav.no
authors: Øystein
authors: Ø
authors: Brenna
authors: Marianne W
authors: MW
authors: Furnes
authors: Ignat
authors: I
authors: Drozdov
authors: Atle
authors: A
authors: van Beelen Granlund
authors: Arnar
authors: A
authors: Flatberg
authors: Arne K
authors: AK
authors: Sandvik
authors: Rosalie T M
authors: RT
authors: Zwiggelaar
authors: Ronald
authors: R
authors: Mårvik
authors: Ivar S
authors: IS
authors: Nordrum
authors: Mark
authors: M
authors: Kidd
authors: Björn I
authors: BI
authors: Gustafsson
mesh_terms: D000818:Animals; D001706:Biopsy; D003113:Colonoscopy; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015203:Reproducibility of Results; D059467:Transcriptome; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects
chemical_list: D014302:Trinitrobenzenesulfonic Acid
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