IGF2BP3通过调节铁亡作用,参与了复发性自发性流产的病变发生
Fangfang Dai1, Yuwei Zhang2, Zhimin Deng1
1Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, People's Republic of China.
Journal of reproductive immunology
|July 25, 2024
概括
胰岛素样生长因子2 mRNA结合蛋白3 (IGF2BP3) 在复发性自发性流产 (RSA) 中被下调. 降低的IGF2BP3促进铁亡并抑制热囊细胞的入侵,有助于RSA的发病.
科学领域:
- 生殖生物学 生殖生物学
- 细胞生物学 细胞生物学
- 分子医学是分子医学.
背景情况:
- 复发性自发性流产 (RSA) 与受损的热囊细胞入侵有关.
- 已知胰岛素样生长因子2 mRNA结合蛋白3 (IGF2BP3) 影响癌症中的细胞迁移和入侵.
- 目前,IGF2BP3在RSA病变发生中的作用尚不清楚.
研究的目的:
- 研究IGF2BP3在复发性自发性流产 (RSA) 中的表达和功能.
- 阐明IGF2BP3影响热囊细胞行为和RSA发育的分子机制.
主要方法:
- 蛋白质测序,西部斑点,qRT-PCR和RSA和正常怀孕的状组织上的免疫组织化学.
- 对单细胞RNA测序数据 (GSE214607) 的分析,以检测 trofhoblasts 中的 IGF2BP3 表达.
- 使用lentivirus技术建立IGF2BP3淘汰HTR-8/SVneo细胞系.
- 用RNA测序来识别IGF2BP3相关的途径.
- 功能性试验评估了热细胞的亡,迁移和铁亡.
- 构建一个LPS诱导的堕胎动物模型来评估胎盘IGF2BP3表达.
主要成果:
- 在RSA患者的小组织和侵入性热囊细胞中,IGF2BP3的表达显著下调.
- IGF2BP3 knockdown 损害了 trofhoblast 迁移,并诱导了细胞亡.
- 从机制上讲,IGF2BP3的淘汰降低了GPX4mRNA的稳定性,促进了铁亡.
- 在LPS诱导堕胎模型中的胎盘组织中也观察到IGF2BP3的下调.
结论:
- 在复发性自发性流产 (RSA) 中,IGF2BP3的下调.
- 降低的IGF2BP3通过促进GPX4介导的铁亡,并抑制 trofhoblast入侵和迁移,有助于RSA.
- IGF2BP3代表了RSA的潜在治疗标.
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