Deoxycholate-induced colitis is markedly attenuated in Nos2 knockout mice in association with modulation of gene expression profiles

Harris Bernstein, Hana Holubec, Carol Bernstein, Natalia A. Ignatenko, Eugene Gerner, Katerina Dvorak, David Besselsen, Karen Ann Blohm-Mangone, Jose Padilla-Torres, Barbora Dvorakova, Harinder Garewal, Claire M. Payne

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18 Scopus citations

Abstract

Nos2 knockout mice were compared to wild-type mice for susceptibility to colitis in response to a diet supplemented with deoxycholate, a bile acid increased in the colon of individuals on a high-fat diet. Wild-type mice fed a fat-related diet, supplemented with 0.2% DOC, develop colonic inflammation associated with increases in nitrosative stress, proliferation, oxidative DNA/RNA damage, and angiogenesis, as well as altered expression of numerous genes. However, Nos2 knockout mice fed a diet supplemented with deoxycholate were resistant to these alterations. In particular, 35 genes were identified whose expression was significantly altered at the mRNA level in deoxycholate-fed Nos2(+/+) mice but not in deoxycholate-fed Nos2(-/-) mice. Some of these alterations in NOS2-dependent gene expression correspond to those reported in human inflammatory bowel disease. Overall, our results indicate that NOS2 expression is necessary for the development of deoxycholate-induced colitis in mice, a unique dietary-related model of colitis.

Original languageEnglish (US)
Pages (from-to)628-642
Number of pages15
JournalDigestive Diseases and Sciences
Volume52
Issue number3
DOIs
StatePublished - Mar 1 2007

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Keywords

  • Colitis
  • Colon cancer
  • Deoxycholate
  • Inflammatory bowel disease
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

Bernstein, H., Holubec, H., Bernstein, C., Ignatenko, N. A., Gerner, E., Dvorak, K., Besselsen, D., Blohm-Mangone, K. A., Padilla-Torres, J., Dvorakova, B., Garewal, H., & Payne, C. M. (2007). Deoxycholate-induced colitis is markedly attenuated in Nos2 knockout mice in association with modulation of gene expression profiles. Digestive Diseases and Sciences, 52(3), 628-642. https://doi.org/10.1007/s10620-006-9608-0