title: Unique dietary-related mouse model of colitis.
abstract: BACKGROUND
  A high-fat diet is a risk factor for the development of inflammatory bowel disease (IBD) in humans. Deoxycholate (DOC) is increased in the colonic contents in response to a high-fat diet. Thus, an elevated level of DOC in the colonic lumen may play a role in the natural course of development of IBD.
  
  
  METHODS
  Wild-type B6.129 mice were fed an AIN-93G diet, either supplemented with 0.2% DOC or unsupplemented and sacrificed at 1 week, 1 month, 3 months, 4 months, and 8 months. Colon samples were assessed by histopathological, immunohistochemical, and cDNA microarray analyses.
  
  
  RESULTS
  Mice fed the DOC-supplemented diet developed focal areas of colonic inflammation associated with increases in angiogenesis, nitrosative stress, DNA/RNA damage, and proliferation. Genes that play a central role in inflammation and angiogenesis and other related processes such as epithelial barrier function, oxidative stress, apoptosis, cell proliferation/cell cycle/DNA repair, membrane transport, and the ubiquitin-proteasome pathway showed altered expression in the DOC-fed mice compared with the control mice. Changes in expression of individual genes (increases or reductions) correlated over time. These changes were greatest 1 month after the start of DOC feeding.
  
  
  CONCLUSIONS
  The results suggest that exposure of the colonic mucosa to DOC may be a key etiologic factor in IBD. The DOC-fed mouse model may reflect the natural course of development of colitis/IBD in humans, and thus may be useful for determining new preventive strategies and lifestyle changes in affected individuals.
authors.affiliation: Department of Cell Biology and Anatomy, College of Medicine, Tucson, AZ 85724, USA. bernstein3@earthlink.net
authors.forename: Harris
authors.initials: H
authors.lastname: Bernstein
authors.forename: Hana
authors.initials: H
authors.lastname: Holubec
authors.forename: Carol
authors.initials: C
authors.lastname: Bernstein
authors.forename: Natalia
authors.initials: N
authors.lastname: Ignatenko
authors.forename: Eugene
authors.initials: E
authors.lastname: Gerner
authors.forename: Katerina
authors.initials: K
authors.lastname: Dvorak
authors.forename: David
authors.initials: D
authors.lastname: Besselsen
authors.forename: Lois
authors.initials: L
authors.lastname: Ramsey
authors.forename: Monique
authors.initials: M
authors.lastname: Dall'Agnol
authors.forename: Karen Ann
authors.initials: KA
authors.lastname: Blohm-Mangone
authors.forename: Jose
authors.initials: J
authors.lastname: Padilla-Torres
authors.forename: Haiyan
authors.initials: H
authors.lastname: Cui
authors.forename: Harinder
authors.initials: H
authors.lastname: Garewal
authors.forename: Claire Margaret
authors.initials: CM
authors.lastname: Payne
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D003092:Colitis / Q000209:etiology* / Q000473:pathology; D004247:DNA / Q000235:genetics; D004041:Dietary Fats / Q000633:toxicity*; D004195:Disease Models, Animal; D018450:Disease Progression; D005500:Follow-Up Studies; D015870:Gene Expression; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics
chemical_list: D004041:Dietary Fats; D018809:Proliferating Cell Nuclear Antigen; D004247:DNA