孕激素受体膜组件2对于人类胎盘外性热囊细胞入侵至关重要
Tae Yokouchi-Konishi1,2, Yongjie Liu3, Liping Feng1
1Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, USA.
Biology of reproduction
|September 4, 2023
概括
降低孕激素受体膜组件2增强了外性热囊细胞的入侵和扩散. 这通过激活缺氧诱导因子1-alpha信号传递发生,这对于正常的胎盘至关重要.
科学领域:
- 生殖生物学 生殖生物学
- 细胞和分子医学是细胞和分子医学.
- 发展生物学 发展生物学
背景情况:
- 适当的外性热囊细胞 (EVT) 侵袭对于成功的胎盘和怀孕至关重要.
- 控制细胞质细胞分化成EVT的分子机制仍然不完全理解.
- 孕激素受体膜组件2 (PGRMC2) 在胎盘热囊细胞亚型中表现不同,这表明其功能角色各不相同.
研究的目的:
- 调查孕激素受体膜组件2 (PGRMC2) 在调节外性热囊细胞 (EVT) 侵袭中的作用.
- 阐明细胞内和细胞外信号通路在PGRMC2介导的EVT入侵中的参与.
- 了解PGRMC2调制对热囊细胞增殖,入侵和血管生成的影响.
主要方法:
- 已建立的HTR8/SVneo细胞 (第一季度EVT模型) 具有使用小干扰RNA或等离子体的PGRMC2淘汰或过度表达.
- 在PGRMC2操纵后分析了细胞形态,增殖,入侵和管形成.
- 评估了缺氧诱导因子1-alpha (HIF-1α) 的激活和血管内皮生长因子A (VEGF-A) 的表达.
- 评估了来自PGRMC2调制细胞的条件介质对EVT入侵的影响.
主要成果:
- 在HTR8/SVneo细胞中,PGRMC2的敲击导致细胞形态变化,增殖和增强的入侵.
- 击败PGRMC2促进了管形成,表明有血管性效应.
- 这些亲侵入性和增殖性影响与低氧诱导因子1-alpha (HIF-1α) 的激活和血管内皮生长因子A (VEGF-A) 表达的增加有关.
- 在这个模型中,通过培养超级生物评估的细胞外信号,并没有显著影响EVT入侵.
结论:
- 孕激素受体膜组件2 (PGRMC2) 的减弱促进了外性热囊细胞 (EVT) 的增殖,入侵和血管生成.
- 在胎盘中PGRMC2的作用是通过激活缺氧诱导因子1-alpha (HIF-1α) 信号的调解.
- 这项研究确定了PGRMC2在热囊细胞入侵中的新功能,为胎盘发育机制提供了洞察力.
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