Regeneration of intestinal mucosa and molecular mechanism of the failure of intestinal epithelial cells under intestinal inflammation.

肠道炎症条件下肠黏膜再生及肠上皮细胞衰竭的分子机制。

• 批准号: 19209027
• 负责人: WATANABE Mamoru
• 金额: $ 31.37万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19209027/
• 关键词: 腸管再生; Wntシグナル; Notchシグナル; Atoh1; 炎症性腸疾患; Wnt; Notch

Significant results were provided as we showed it in this study as follows.1) We showed that the up-regulation of Notch signal in inflammatory bowel disease was necessary to promote cell proliferation to maintain mucosal barrier with a sacrifice of differentiation state.2) We identified Hes1 as the critical gene to suppress the differentiation of intestinal mucosa under the Notch signal stimulation in inflammatory bowel disease, using microarray examination.3) We showed that Hes1 protein is highly expressed on the chronic inflammation mucosa under the Notch signal up-regulation in inflammatory bowel disease.4) Hes1 suppress goblet cell differentiation by the repression of Hath1 gene transcription.5) Hes1 directly binds to the 5' promoter region of Hath1 resulting in the suppression of Hath1 gene expression, using ChIP assay.

研究结果表明：1)在炎症性肠病中，Notch信号的上调是促进细胞增殖以维持黏膜屏障的必需因素，但以牺牲分化状态为代价。2)我们确定Hes1是在Notch信号刺激下抑制炎症性肠病肠粘膜分化的关键基因。3)我们发现Hes1蛋白在炎症性肠病的慢性炎症黏膜上高表达。4)Hes1通过抑制Hath1基因转录抑制杯状细胞的分化。5)Hes1直接与Hath1的5‘启动子区域结合，从而抑制Hath1基因的表达。

项目成果

A single polymorphic amino acid on Toxoplasma gondii kinase ROP16 determines the direct and strain-specific activation of Stat3.

• DOI: 10.1084/jem.20091703
• 发表时间: 2009-11-23
• 期刊: The Journal of experimental medicine
• 作者: Yamamoto M;Standley DM;Takashima S;Saiga H;Okuyama M;Kayama H;Kubo E;Ito H;Takaura M;Matsuda T;Soldati-Favre D;Takeda K
• 通讯作者: Takeda K

The role of human transcription elongation factor DSIF in the suppression of senescence and apoptosis

人转录延伸因子DSIF在抑制衰老和凋亡中的作用

• 发表时间: 2009
• 期刊: Genes Cells. 14
• 作者: Komori K;Inukai N;Yamada T;Yamaguchi Y;Handa H
• 通讯作者: Handa H

Emerging issues in inflammatory bowel diseases

炎症性肠病的新问题

• 发表时间: 2007
• 作者: Yamamoto S;Kawamata M;Nishiyama S;Wakuda T;Takei N;Mori N;Tsukada H.;渡辺守
• 通讯作者: 渡辺守

Hepatitis delta antigen binds to the clamp of RNA polymerase II and affects transcriptional fidelity

丁型肝炎抗原与 RNA 聚合酶 II 钳结合并影响转录保真度

• 发表时间: 2007
• 期刊: Genes Cells. 12
• 作者: Yamaguchi Y;Mura T;Chanarat S;Okamoto S;Handa H
• 通讯作者: Handa H

Commensal bacteria-derived ATP mediates development of intestinal Th17 cells

共生细菌来源的 ATP 介导肠道 Th17 细胞的发育

• 发表时间: 2009
• 作者: 青戸隆博;西村栄美;Kiyoshi Takeda
• 通讯作者: Kiyoshi Takeda