环SOD2:通过调节miR-378g/Snail1轴来调节性结肠炎中肠粘膜屏障功能的破坏
Guannan Ye1, Jiayi Zhang1, Jin Peng1
1Department of Gastroenterology, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Journal of gastroenterology and hepatology
|April 22, 2024
概括
循环SOD2 (circSOD2) 通过miR-378g/Snail1通道损害肠道屏障,使性结肠炎恶化. 减少circSOD2表达可以在性结肠炎的细胞和老鼠模型中修复这种屏障.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 性结肠炎 (UC) 涉及肠粘膜屏障功能障碍.
- 循环RNAs (circRNAs) 涉及UC病变发生.
- 在UC中circSOD2的具体作用尚不清楚.
研究的目的:
- 研究circSOD2在UC中的作用.
- 阐明circSOD2在调节肠粘膜屏障功能的分子机制.
- 评估circSOD2作为UC的潜在治疗点.
主要方法:
- 利用脂聚糖 (LPS) 诱导的Caco2细胞和硫酸 (DSS) 诱导的鼠标模型来模仿UC.
- 使用RT-qPCR进行量化circSOD2,miR-378g和Snail1表达.
- 评估了细胞活力,炎症性细胞因子,屏障完整性 (TEER,FITC-dextran透性) 和蛋白质水平 (Snail1,Zo-1,Claudin2).
- 通过双露西法酶记者测定证实了分子相互作用.
主要成果:
- 在UC患者和模型中,CircSOD2被上调.
- 抑制circSOD2提高了细胞活力,屏障功能,并减少了LPS诱导的Caco2细胞中的炎症.
- CircSOD2作为miR-378g的分子海绵,对Snail1的表达进行上调.
- 在细胞和老鼠模型中,通过miR-378g/Snail1轴,circSOD2敲除改善了UC相关的肠壁损伤.
结论:
- 在UC中,CircSOD2加剧了肠粘膜屏障功能障碍.
- 环SOD2/miR-378g/Snail1轴是驱动UC进展的关键机制.
- 向circSOD2可能为性结肠炎提供治疗策略.
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