| Project/Area Number |
21590405
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
OKAYASU Isao 北里大学, 医学部, 教授 (20014342)
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| Project Period (FY) |
2009 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 潰瘍性大腸炎 / 分子病理 / UC / CITED2 / 炎症 |
|---|
| Research Abstract |
In ulcerative colitis, Fusobacterium varium is significantly detected in patients' mucosa, and butyric acid, abundantly produced by the bacterium, induces epithelial apoptosis. Here, we identified a gene induced by butyric acid specifically in ulcerative colitis-associated cancer cell lines. cDNA microarray and the validation study revealed CITED2 to be specifically upregulated. CITED2 could be shown to induce p53 acetylation and p53-dependent apoptosis, accompanied by binding of CBP/p300.In inflammatory foci of ulcerative colitis, histologically evident inflammatory activity and CITED2 expression were significantly correlated. On the other hand, we also found olfactomedin 4(OLFM4) induced in the UC-patients' colonic mucosae, and its expression is correlated to the histological activity of UC. In conclusion, CITED2 was identified as ulcerative colitis-associated protein by cDNA microarray based on the Percellome method under UC-mimicking conditions in vitro. CITED2 activation may induce mucosal apoptosis and erosion by activating p53 and thus play a critical role in linking enteric bacteria with mucosal inflammation in ulcerative colitis. Further study of association of CITED2 and OLFM4 is remains to be clarified.
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