通过调节ROS/BRD4/PI3K/YAP/PIGF信号诱导血管生成,SHP2改善了晚期发作的胎儿生长限制
1Department of Obstetrics, Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, China.
PloS one
|February 13, 2026
概括
SHP2蛋白通过调节内皮前细胞 (EPC) 中的ROS/BRD4和PI3K/YAP/PIGF通路来增强晚发胎儿生长限制 (LO-FGR),改善其血管生成潜力和功能.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 晚期发作的胎儿生长限制 (LO-FGR) 对怀孕结果构成重大风险.
- 了解LO-FGR背后的分子机制对于开发有效干预措施至关重要.
- SHP2 (一种蛋白质氨酸酸酶) 已成为各种细胞过程中的潜在关键调节剂.
研究的目的:
- 研究SHP2在晚期发作的胎儿生长限制 (LO-FGR) 中的作用和分子机制.
- 在LO-FGR条件下,阐明由内皮原生细胞 (EPC) 中SHP2调节的信号通路.
主要方法:
- 对GSE147776数据集的生物信息学分析,以确定差异表达基因 (DEG) 和信号通路.
- 在实验室实验中使用在模拟的LO-FGR条件下培养的EPC.
- 使用特定药物 (JQ-1,PHPS1,Verteporfin) 操纵SHP2活性和抑制BRD4.
- 西部布洛特分析,管形成试验,殖民地形成试验和流动细胞测量来评估蛋白质表达,细胞增殖,细胞周期和细胞亡.
主要成果:
- 生物信息学分析揭示了和河马信号通路的丰富性,SHP2显示了与关键信号分子的特定相关性.
- LO-FGR条件导致NOX4和核BRD4的增加,SHP2酸化和亲血管性因素的减少,EPC增殖的减少和亡的增加.
- 抑制BRD4 (使用JQ-1) 逆转了这些效应,增加了SHP2酸化,亲血管性因素,EPC增殖和G2阶段细胞周期停止,同时减少了细胞亡.
- 抑制SHP2模仿了LO-FGR表型,证实了它的关键作用.
结论:
- SHP2在改善LO-FGR方面发挥着至关重要的作用.
- SHP2通过调节ROS/BRD4和PI3K/YAP/PIGF信号通路来发挥其保护作用.
- 向SHP2可能通过增强内皮前细胞功能和血管生成来提供管理LO-FGR的治疗策略.
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