TWEAK is involved in DNA damage in intestinal epithelial cells

TWEAK 参与肠上皮细胞 DNA 损伤

• 批准号: 23590955
• 负责人: DOHI Taeko
• 金额: $ 3.24万
• 依托单位: Research Institute, International Medical Center of Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590955/
• 关键词: 消化管上皮細胞; TWEAK; Fn14; DNA傷害; 炎症; 消化管炎症; TNFSF; レトロトランスポジション; TNFSP

TNF-like weak inducer of apoptosis (TWEAK) is a member of TNF superfamily (TNFSF). Its receptor FGF-inducible molecule-14 (Fn14) has been identified. DNA damage is induced by gamma-irradiation and anti-cancer drugs. Gastrointestinal mucosal damage is one of the most significant side-effects of these treatments, which limits the dose of treatment. In this study, we found that TWEAK/Fn14 pathway is significantly involved in the DNA damage of intestinal mucosa that induced by gamma-irradiation and some type of anti-cancer drugs. Particularly, TWEAK enhances death signal mediated by Tumor necrosis factor (TNF)-alfa. results suggest the possible application of TWEAK inhibitors to prevent mucosal damage in cancer therapy.

肿瘤坏死因子样弱凋亡诱导因子（TWEAK）是肿瘤坏死因子超家族（TNFSF）的成员。其受体FGF诱导分子14（Fn 14）已被鉴定。DNA损伤是由γ射线和抗癌药物引起的。胃肠道粘膜损伤是这些治疗的最显著的副作用之一，这限制了治疗的剂量。本研究发现TWEAK/Fn 14信号通路在γ射线和某些抗癌药物诱导的肠粘膜DNA损伤中起重要作用。特别地，TWEAK增强由肿瘤坏死因子（TNF）-α介导的死亡信号。结果提示TWEAK抑制剂在癌症治疗中预防粘膜损伤的可能应用。

项目成果

TWEAK/Fn14 pathway promotes chronic colitis and fibrosis mediated by IL-13-TSLP axis.

TWEAK/Fn14 通路促进 IL-13-TSLP 轴介导的慢性结肠炎和纤维化。

• 作者: Dohi T;Kawamura YI;Kawashima R;Son A;Oshio T;Wu P;Burkly LC.
• 通讯作者: Burkly LC.

IL-13 induces TWEAK-dependent activation of TNF- and intestinal epithelial cell damage –a pathway associated with ulcerative colitis

IL-13 诱导 TNF-α 的 TWEAK 依赖性激活和肠上皮细胞损伤——与溃疡性结肠炎相关的途径

• 发表时间: 2012
• 作者: T Dohi;R Kawashima;YI Kawamura;T Oshio;M Yamazaki;T Hagiwara;T Okada;P Wu;S Szak;YJ Kawamura;F Konishi;O Miyake;H Yano;Y Saito;L. C. Burkly
• 通讯作者: L. C. Burkly

IL-13による消化管粘膜傷害におけるTWEAK / Fn14経路の関連性

TWEAK/Fn14通路在IL-13诱导的胃肠粘膜损伤中的相关性

• 作者: 川島麗;土肥多惠子;河村由紀;川上文貴;市川尊文
• 通讯作者: 市川尊文

Involvement of L1 retrotransposition in murine experimental colitis-cancer model

L1 逆转录转座参与小鼠实验性结肠炎-癌症模型

• 发表时间: 2013
• 作者: Otusbo T;Kawamura YI;Ishizaka Y;Dohi T
• 通讯作者: Dohi T

Cell type-specific, genome-wide epigenetic analysis for lamina propria cells isolated from the colon with ulcerative colitis.

对从溃疡性结肠炎结肠中分离出的固有层细胞进行细胞类型特异性、全基因组表观遗传分析。

• 作者: Otsubo T;Kawamura YI;Dohi T.
• 通讯作者: Dohi T.