期刊
DIGESTIVE DISEASES AND SCIENCES
卷 52, 期 3, 页码 628-642出版社
SPRINGER
DOI: 10.1007/s10620-006-9608-0
关键词
colitis; nitric oxide synthase; deoxycholate; inflammatory bowel disease; colon cancer
资金
- NCI NIH HHS [1R21CA111513-01A1, 1P50CA95060-01, P01 CA072008, CA72008, CA23074] Funding Source: Medline
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.
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