同类氨酸通过PGE2/STAT3信号通路促进大肠炎小鼠的肠道炎症
Akang Shao1,2, Qiu Zhao1,2, Min Chen3,4
1Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Donghu Road 169, Wuhan, 430071, People's Republic of China.
超homocysteinemia恶化结肠炎通过促进T辅助17 (Th17) 细胞通过前列腺素E2 (PGE2) 和信号转换器和转录3 (STAT3) 途径的激活器分化. 这项研究阐明了结肠炎中Th17细胞增殖背后的机制.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 生物化学 生化学
背景情况:
- 之前的研究通过T辅助17 (Th17) 细胞分化将同类氨酸 (Hcy) 与恶化DSS诱导的大肠炎联系起来.
- 在Th17细胞分化中Hcy的作用背后的精确分子机制仍然不清楚.
研究的目的:
- 在结肠炎的背景下阐明Hcy促进Th17细胞分化的信号通路.
主要方法:
- 建立了大肠炎 (DSS) 和高homocysteinemia (甲素) 的BALB/c小鼠模型.
- 通过ELISA测量Hcy和前列腺素E2 (PGE2) 的度.
- 关键信号分子 (cPLA2,COX2,cAMP,STAT3,IL-17A,RORγt) 的蛋白质表达被分析使用西欧布洛特.
主要成果:
- 抑制COX降低了PGE2,cAMP和p-STAT3水平,这表明PGE2在STAT3.3的上游作用.
- STAT3抑制显著降低了IL-17A和RORγt的表达.
- 联合抑制COX和STAT3通路显著降低了Th17细胞分化标记物 (IL-17A,RORγt,IL-23R).
结论:
- 过高homocysteinemia通过增强Th17细胞分化和增殖来加剧DSS诱导的大肠炎.
- 确定PGE2/STAT3信号通路是调解Hcy在结肠炎中的炎症促成作用的关键机制.
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