MANF通过与NPM1相互作用并降低对 trofhoblast 细胞迁移和入侵的调节,促进无法解释的反复流产
Yuan Fang1,2,3,4, Junhui Zhang1,2,3,4, Damin Zhu1,3,4
1Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei 230022, Anhui, China.
International journal of biological sciences
|January 2, 2024
概括
中脑星细胞衍生神经变因子 (MANF) 在不明原因的反复流产 (URM) 中升高. MANF通过降解核胺1 (NPM1),激活p53,并抑制 trofhoblast 功能来触发流产.
科学领域:
- 生殖生物学 生殖生物学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 无法解释的反复流产 (URM) 与热囊细胞缺陷有关.
- 中脑星细胞衍生神经变因子 (MANF) 影响细胞迁移和入侵.
- 人们对MANF在怀孕障碍中的作用尚不清楚.
研究的目的:
- 调查MANF在无法解释的反复流产 (URM) 中的作用.
- 阐明MANF在URM中影响 trofhoblast 功能的分子机制.
主要方法:
- 在URM患者的血液和组织中量化MANF水平.
- 在热囊细胞中分析MANF-核胺1 (NPM1) 相互作用.
- 对p53信号通路激活的评估.
- 使用URM小鼠模型进行体内研究.
主要成果:
- 与对照组相比,URM患者的MANF水平较高.
- 在URM trofhoblasts中,MANF与NPM1相互作用,促进NPM1的无处不在和降解.
- 这种相互作用对p53通路进行上调,抑制了热囊细胞的增殖,迁移和入侵.
- 在小鼠中,MANF下调降低了胎儿再吸收,而NPM1下调增加了堕胎率.
结论:
- 通过降低NPM1的调节和激活p53.3,MANF有助于URM中流产.
- MANF-NPM1相互作用是URM病变发生的一个关键机制.
- 针对MANF或MANF-NPM1相互作用可能为URM提供治疗策略.
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