Role of CITED2, a novel ulcerative colitis specific gene, to colitis and carcinogenesis.

CITED2（一种新型溃疡性结肠炎特异性基因）在结肠炎和癌发生中的作用。

• 批准号: 21590405
• 负责人: YOSHIDA Tsutomu
• 金额: $ 3万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590405/
• 关键词: 潰瘍性大腸炎; 分子病理; UC; CITED2; 炎症

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.

在溃疡性结肠炎中，在患者的粘膜和丁酸酸中显着检测到螺杆的差异，并通过细菌大量产生，诱导上皮细胞凋亡。在这里，我们鉴定了一个由胰酸酯诱导的基因，该基因在溃疡性结肠炎相关的癌细胞系中。 cDNA微阵列和验证研究表明，引用2被明确上调。可以证明Cited2可以诱导p53乙酰化和p53依赖性凋亡，并伴有CBP/p300的结合。在溃疡性结肠炎的炎症灶，组织学证明炎症活性和CUSITED2表达显着相关。另一方面，我们还发现在UC患者的结肠粘膜病中诱导的嗅觉素4（OLFM4），其表达与UC的组织学活性相关。总之，基于cDNA微阵列，基于Percellome方法在UC模仿条件下，CID2被鉴定为溃疡性结肠炎相关的蛋白。引用2激活可能通过激活p53诱导粘膜凋亡和侵蚀，因此在将肠细菌与溃疡性结肠炎中的粘膜炎症联系起来中起着至关重要的作用。进一步研究Cucited2和OLFM4的关联尚待澄清。

项目成果

CITED2 is activated in ulcerative colitis and induces p53-dependent apoptosis in response to butyric acid

• DOI: 10.1007/s00535-010-0355-9
• 发表时间: 2011-03-01
• 期刊: JOURNAL OF GASTROENTEROLOGY
• 影响因子: 6.3
• 作者: Yoshida, Tsutomu;Sekine, Tsukasa;Okayasu, Isao
• 通讯作者: Okayasu, Isao

Mucosal Remodeling and Alteration of Stromal Microenvironment in Ulcerative Colitis as Related to Colorectal Tumorigenesis

• DOI: 10.5772/25362
• 发表时间: 2011-12
• 作者: I. Okayasu;Tsutomu Yoshida;T. Mikami;J. Mitsuhashi;M. Ichinoe;N. Yanagisawa;W. Tokuyama;Kiyomi Hana;Y. Ishibashi

Significance of gene expression and localization in active and inactive ulcerative colitis by comprehensive analysis

综合分析活动性和非活动性溃疡性结肠炎基因表达和定位的意义

• 发表时间: 2009
• 作者: Miyamae Y;Yoshida T;Okayasu I.
• 通讯作者: Okayasu I.

大腸腸内細菌による粘膜上皮性サイトカイン誘導-潰瘍性大腸炎・炎症機序との関連

大肠肠杆菌诱导粘膜上皮细胞因子与溃疡性结肠炎及炎症机制的关系

• 发表时间: 2009
• 作者: 丸善明;吉田功;田原あづさ;梅沢敦子;大草敏史;岡安勲
• 通讯作者: 岡安勲

Mucosal remodeling in long-standing ulcerative colitis with colorectal neoplasia : Significant alterations of NCAM plus or alpha-SMA plus subepithelial myofibroblasts and interstitial cells

长期溃疡性结肠炎伴结直肠肿瘤的粘膜重塑：NCAM+或α-SMA+上皮下肌成纤维细胞和间质细胞的显着改变

• 发表时间: 2009
• 期刊: Pathol Int
• 影响因子: 2.2
• 作者: Okayasu I;Yoshida;T.;Mikami;T.;Hana;K.;Yokozawa;M.;Araki;K.;Mitsuhashi;J.;Kikuchi;M.;Adachi;E.;Sada;M
• 通讯作者: M