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丁酸盐通过通过MEK4-JNK信号通路激活调节Fut2表达来保护肠道屏障
Dan-Dan Zhang1, Zhao-Xi Huang1, Xiao-Chen Liu1
1Department of Neonatology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Disease in infection and Immunity, Chongqing, China.
外源性酸盐增强了肠道屏障的完整性,并通过通过MEK4-JNK通路调节Fucosyltransferase 2 (Fut2) 表达,在新生小鼠中保护新生儿肠道炎 (NEC).
科学领域:
- 胃肠病学和新生儿医学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 结核性肠球炎 (NEC) 是一种严重的,危及生命的胃肠道炎症疾病,影响新生儿.
- 可转移酶2 (Fut2) 在肠上皮细胞可化中起着关键作用,影响肠道健康.
- 了解调节Fut2的机制对于开发NEC疗法至关重要.
研究的目的:
- 为了研究丁酸盐如何影响Fucosyltransferase 2 (Fut2) 表达.
- 阐明分子机制,特别是MEK4-JNK通路,参与酸盐介导的Fut2调节.
- 评估丁酸盐在预防NEC方面的治疗潜力.
主要方法:
- 使用了NEC的体内和体外模型.
- 给药的丁酸盐和使用的途径调节剂 (SP600125 抑制,异胺激活 MEK4-JNK 途径).
- 评估了Fut2,ocludin,ZO-1和关键的MEK4-JNK通路蛋白 (p-MEK4,p-JNK,p-c-jun) 的表达,这些蛋白通过西部涂抹.
- 使用FITC-Dextran试验测量肠道透率.
主要成果:
- 外源性酸盐在NEC模型中显著上调了Fut2,ocludin和ZO-1表达.
- 丁酸盐的使用在体内减少了肠道的透性.
- 丁酸盐激活了MEK4-JNK通路,这是MEK4,JNK和c-jun的酸化增加所证明的.
- 抑制MEK4-JNK通路 (SP600125) 逆转了丁酸盐的作用,而激活 (亚尼索米辛) 则模仿了它们.
结论:
- 丁酸盐通过激活MEK4-JNK信号通路来提高Fut2表达的调节.
- 酸盐补充剂改善了肠道屏障的完整性,并保护新生小鼠免受NEC.
- 这项研究为治疗性使用丁酸盐来管理NEC提供了机制基础.
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