TRIP6 promotes inflammatory damage via the activation of TRAF6 signaling in a murine model of DSS-induced colitis.
TRIP6 promotes inflammatory damage via the activation of TRAF6 signaling in a murine model of DSS-induced colitis.
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在 DSS 诱导的结肠炎小鼠模型中，TRIP6 通过激活 TRAF6 信号传导促进炎症损伤
DOI：
10.1186/s12950-021-00298-0
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发表时间：
2022-01-04
期刊：
影响因子：
--
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Yang Y;Li XM;Wang JR;Li Y;Ye WL;Wang Y;Liu YX;Deng ZY;Gan WJ;Wu H
背景trip6是一种酶家族成员，作为一种适应蛋白调节多种生物过程。在之前的报道中，TRIP6被证明在调节炎症中发挥作用。然而，其在结肠炎中的体内作用和机制重要性在很大程度上仍然难以捉摸。因此，我们采用了TRIP6缺陷（TRIP6−/−）小鼠，以探索TRIP6在右旋糖酐硫酸钠（DSS）诱导的小鼠结肠炎模型中的机制重要性。与TRIP6 - / -小鼠相比，野生型（TRIP6+/+）小鼠在dss介导的疾病诱导后出现更严重的结肠炎，这可以通过更严重的结肠炎症和相关的隐窝损伤来证明。DSS处理后，野生型小鼠的TRIP6表达显著升高。从机制上讲，TRIP6与TRAF6结合并增强TRAF6的寡聚和自泛素化。这导致体内结肠炎小鼠模型中NF-κB信号的激活和促炎细胞因子如TNFα和IL-6的表达。这些体内数据表明，TRIP6通过与TRAF6的相互作用，激活炎症性TRAF6信号，作为dss诱导的结肠炎的积极调节因子，突出了其作为一种理论上可以靶向预防或治疗结肠炎的蛋白的治疗前景。
BackgroundTRIP6 is a zyxin family member that serves as an adaptor protein to regulate diverse biological processes. In prior reports, TRIP6 was shown to play a role in regulating inflammation. However, its in vivo roles and mechanistic importance in colitis remain largely elusive. Herein, we therefore employed TRIP6-deficient (TRIP6−/−) mice in order to explore the mechanistic importance of TRIP6 in a dextran sodium sulfate (DSS)-induced model of murine colitis.FindingsWild-type (TRIP6+/+) mice developed more severe colitis following DSS-mediated disease induction relative to TRIP6−/−mice, as evidenced by more severe colonic inflammation and associated crypt damage. TRIP6 expression in wild-type mice was significantly elevated following DSS treatment. Mechanistically, TRIP6 binds to TRAF6 and enhances oligomerization and autoubiquitination of TRAF6. This leads to the activation of NF-κB signaling and the expression of pro-inflammatory cytokines such as TNFα and IL-6, in the in vivo mouse model of colitis.ConclusionsThese in vivo data demonstrate that TRIP6 serves as a positive regulator of DSS-induced colitis through interactions with TRAF6 resulting in the activation of inflammatory TRAF6 signaling, highlighting its therapeutic promise as a protein that theoretically can be targeted to prevent or treat colitis.
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