通过NEAT1/CTCF/MUC19轴,METTL3加剧了Streptococcus pneumoniae诱导的细胞损伤
Dong-Bo Ma1, Hui Zhang1, Xi-Ling Wang1
1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, China.
The Kaohsiung journal of medical sciences
|May 17, 2024
概括
甲基转移酶类3 (METTL3) 通过上调NEAT1,CTCF和MUC19.3来加剧Streptococcus pneumoniae引起的肺损伤. 降低METTL3的调节缓解了膜上皮细胞的亡和炎症.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 气膜屏障的破坏是急性肺损伤的一个关键因素.
- 肺炎链球菌 (SP) 感染可能导致严重的肺损伤.
研究的目的:
- 研究甲基转移酶类3 (METTL3) 在SP诱导的亡和膜上皮细胞 (AEC) 炎症中的作用.
- 阐明涉及METTL3,NEAT1,CTCF和MUC19在SP诱导的肺损伤中的分子机制.
主要方法:
- AECs被培养并感染了SP.
- 基因和蛋白质表达水平使用qRT-PCR,西部斑块和ELISA进行了分析.
- 评估了N6-甲基氨酸 (m6A) 修饰,NEAT1亚细胞局部化和NEAT1-CTCF结合.
- 使用甲基化RNA免疫沉-qPCR.
主要成果:
- 在AEC中,SP感染上调了METTL3表达,诱导了apoptosis和炎症.
- 降低METTL3的调节减少了SP诱导的亡和炎症.
- 通过METTL3介导的m6A修饰增加了NEAT1,从而促进了它与CTCF的结合,从而促进了MUC19的转录.
- 过度表达NEAT1或MUC19加剧了SP诱导的细胞损伤.
结论:
- METTL3在加重SP引起的肺损伤方面发挥着关键作用.
- METTL3-NEAT1-CTCF-MUC19轴是一种新的途径,有助于SP诱导的AEC中的亡和炎症.
- 准METTL3通路可能为SP造成的急性肺损伤提供治疗策略.
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