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.

溃疡性结肠炎患者的黏膜中大量检测到不同的梭杆菌，而该细菌大量产生的丁酸可诱导上皮细胞凋亡。在这里，我们在溃疡性结肠炎相关的癌细胞系中发现了一个由丁酸特异性诱导的基因。cDNA芯片和验证研究显示，CITED2是特异性上调的。CITED2可诱导p53乙酰化和p53依赖性细胞凋亡，并伴有CBP/p300的结合。在溃疡性结肠炎炎症灶中，组织学上明显的炎症活性与CITED2表达显著相关。另一方面，我们还发现olfactomedin 4（OLFM4）在UC患者结肠黏膜中诱导表达，其表达与UC的组织学活性相关。综上所述，在体外模拟uc条件下，基于Percellome方法的cDNA芯片鉴定出CITED2为溃疡性结肠炎相关蛋白。CITED2激活可通过激活p53诱导粘膜凋亡和糜烂，在溃疡性结肠炎肠道细菌与粘膜炎症的联系中起关键作用。关于CITED2与OLFM4的关联的进一步研究仍有待明确。

项目成果

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

潰瘍性大腸炎炎症関連蛋白質OLFM4の炎症における役割

溃疡性结肠炎炎症相关蛋白OLFM4在炎症中的作用

• 发表时间: 2011
• 作者: 吉田功;他
• 通讯作者: 他

Mucosal Remodeling and Alteration of Stromal Microenvironment in Ulcerative Colitis as Related to Colorectal Tumorigenesis(p242-245)(Mortimer B.O'Connor eds.)(In Ulcerative Colitis-Epidemiology, Pathogenesis and Complications)

溃疡性结肠炎中与结直肠肿瘤发生相关的粘膜重塑和基质微环境的改变（p242-245）（Mortimer B.OConnor 编辑）（溃疡性结肠炎流行病学、发病机制和并发症）

• 发表时间: 2011
• 作者: Okayasu;I.;et al
• 通讯作者: et al

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.