通过调节miR-374b-5p/SRSF7轴,METTL3促进缺血-再输液损伤
Kun Zhu1, Shirui Sun2, Zepeng Li2,3
1Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
概括
缺血-再输损伤 (IRI) 涉及微RNA-374b-5p (miR-374b-5p),通过抑制细胞活力来促进损伤. 通过调节miR-374b-5p处理,METTL3增强IRI,突出了一个新的m6A甲基化途径.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 缺血-再损伤 (IRI) 是急性损伤的主要原因之一.
- 在脏IRI中,微RNA-374b-5p (miR-374b-5p) 的特定调节机制尚不清楚.
研究的目的:
- 研究miR-374b-5p在脏IRI中的作用.
- 阐明涉及METTL3,miR-374b-5p和SRSF7在脏IRI中的调节途径.
主要方法:
- 在细胞系 (HK-2,TCMK-1) 和小鼠中建立了低氧/低氧化 (H/R) 和缺血-反 (I/R) 模型.
- 通过CCK-8,流细胞计和TUNEL测定来评估细胞活力和细胞亡.
- 利用双 luciferase 记者,甲基化 RNA 免疫沉降 (MeRIP) 和共同免疫沉降 (Co-IP) 试验来确认分子相互作用.
主要成果:
- miR-374b-5p在H/R诱导的细胞中显著上调,并促进了RTEC损伤.
- SRSF7被确定为miR-374b-5p的直接标,其抑制逆转了miR-374b-5p诱导的损伤.
- METTL3调节了pri-miR-374b-5p处理以m6A依赖的方式,并且METTL3敲击保护免受脏IRI的影响.
结论:
- METTL3通过上调 miR-374b-5p 来促进脏IRI,该调节的目标是SRSF7.
- 这项研究揭示了一个新的m6A甲基化依赖的调节轴 (METTL3/miR-374b-5p/SRSF7) 在脏IRI的发病过程中.
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