在产前症中,WTAP通过依赖于YTHDF2的机制调节NCOA4介导的铁化
Can Li1, Zhiyuan Li2, Chunling Ma1
1Department of Obstetrics and Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, Shandong Province, China.
Clinical epigenetics
|November 19, 2025
概括
通过调节NCOA4降解,WTAP蛋白抑制了孕前 (PE) 中的铁亡. 破坏这种途径会使氧化压力恶化,并对PE的妊娠结果产生不利影响.
科学领域:
- 生殖生物学 生殖生物学
- 分子生物学分子生物学
- 病理学 病理学 病理学
背景情况:
- 孕前 (PE) 是一种与胎盘功能障碍和氧化应激相关的妊娠疾病.
- 细胞中通过m6A修饰调节铁亡的WTAP的作用尚不清楚.
研究的目的:
- 调查WTAP在热囊细胞铁亡中的作用.
- 探索涉及PE中NCOA4和YTHDF2的m6A修饰的机制.
主要方法:
- 在PE胎盘中检查WTAP和m6A水平,使用qRT-PCR,西斑和免疫组织化学.
- 在热囊细胞和PE小鼠模型中操纵了WTAP,NCOA4和YTHDF2.
- 评估了细胞功能,氧化应激,铁亡标志物和m6A修饰.
主要成果:
- 降低PE胎盘中的WTAP和m6A水平与小性损伤相关.
- 通过m6A修饰和YTHDF2结合,WTAP促进了NCOA4mRNA的降解.
- 在体外和体内,NCOA4过度表达加剧了铁和PE症状,而WTAP/YTHDF2下调则恶化了结果.
结论:
- 通过通过依赖YTHDF2的m6A甲基化促进NCOA4降解,WTAP抑制PE中的铁亡.
- 这种途径的破坏加剧了热囊细胞功能障碍和不良妊娠结果.
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