在炎症性肠病中,由巨细胞衍生的外体通过通过mircroRNA-22323调节TMIGD1,促进肠粘膜屏障功能障碍
Xin Chang1, Yi-Hang Song2, Tian Xia2
1Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai, China; Department of Gastroenterology, the General Hospital of Central Theater Command, Wuhan, China.
International immunopharmacology
|June 10, 2023
概括
携带miR-223的巨细胞衍生外体通过破坏肠道屏障,使炎症性肠病 (IBD) 恶化. 这项研究确定miR-223是通过TMIGD1抑制IBD进展的关键参与者.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
背景情况:
- 外基因组调解细胞间的通信,运输微RNA (miRNAs) 对于生物过程至关重要.
- 在炎症性肠病 (IBD) 病原发生过程中,巨细胞衍生的外体的作用仍然在很大程度上未被探索.
研究的目的:
- 在IBD的背景下,研究巨细胞衍生的外体内特定的miRNAs.
- 阐明这些外体miRNAs影响IBD发展的分子机制.
主要方法:
- 建立了一个硫酸 (DSS) 诱导的IBD小鼠模型.
- 从脂聚糖 (LPS) 刺激的小鼠骨髓衍生巨细胞 (BMDMs) 中分离出外体,并进行miRNA测序.
- 利用lentiviruses来操纵miRNA表达,并使用Transwell与老鼠和人类器官的共同培养来在体外模型IBD.
主要成果:
- 由LPS诱导的巨细胞释放出外体,使IBD恶化.
- 米RNA测序确定了miR-223作为一个关键的外体miRNA.
- 在体内和有机体模型中,上调的外体miR-223恶化了肠道屏障功能障碍.
- 确定了TMIGD1作为一个被miR-223抑制的基因,导致屏障功能障碍.
结论:
- 巨细胞衍生出异位体的miR-223在DSS诱导的大肠炎进展中起着重要作用.
- 外基因组miR-223通过抑制与屏障相关的因子TMIGD1.1来诱导肠道屏障功能障碍.
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