滋养细胞来源的外泌体调控ephrinB信号通路介导蜕膜NK细胞在子宫螺旋动脉重铸中的作用的研究

Perfect spiral artery remodeling during pregnancy is of great importance to maternal and fetal health. The most popular theory of spiral artery remodeling nowadays is that both maternal and fetal factors take part in the process. Decidual natural killer (dNK) is the key functional cell in the initiation and establishment of spiral artery remodeling on the maternal side. Exosomes, as biological information carrier, are able to regulate the functions of remote target cells. Studies showed that trophoblast-derived exosomes play an important role in fetus-induced spiral artery remodeling. However, their role in maternal regulatory of spiral artery remodeling remain to be elucidated. Our previous research showed that the activation of ephrinB signaling pathway in dNK related with enhanced dNK functions in spiral artery remodeling. Thus, we infer that trophoblast-derived exosomes have a vital impact on dNK-induced spiral artery remodeling process. This study will discuss the effects of trophoblast-derived exosomes in the regulation of biological functions of dNK in spiral artery remodeling by the activation of ephrinB signaling pathway via cell, co-culture system and animal model, which could provide potential treatment target for related diseases.

完善的子宫螺旋动脉重铸对于妊娠时母胎的健康有着极为重要的意义。目前主流学说认为，子宫螺旋动脉重铸受到母胎因素的共同调节。蜕膜NK细胞是母体方面启动和参与子宫螺旋动脉重铸的关键细胞。外泌体作为稳定的生物信息载体，可以远距离调节靶细胞生物学功能。滋养细胞来源的外泌体参与了胎儿因素对子宫螺旋动脉重铸过程的调节，其对母体因素的影响尚不清楚。我们的前期研究发现激活蜕膜NK细胞中ephrinB信号通路，能够促进蜕膜NK细胞在子宫螺旋动脉重铸中的作用。据此我们推测滋养细胞来源的外泌体通过ephrinB信号通路调节蜕膜NK细胞功能，启动并参与子宫动脉重铸。本研究拟通过细胞、共培养以及动物模型多个层面，全面探讨滋养细胞来源的外泌体通过ephrinB信号通路介导蜕膜NK细胞在子宫螺旋动脉重铸过程中的作用，力求为相关疾病的防治提供潜在的治疗靶点。

完善的子宫螺旋动脉重铸对于妊娠时母胎的健康有着极为重要的意义。目前主流学说认为，子宫螺旋动脉重铸受到母胎因素的共同调节。蜕膜NK细胞是母体方面启动和参与子宫螺旋动脉重铸的关键细胞。外泌体作为稳定的生物信息载体，可以远距离调节靶细胞生物学功能。滋养细胞来源的外泌体参与了胎儿因素对子宫螺旋动脉重铸过程的调节，其对母体因素的影响尚不清楚。.本项目研究延续前期研究，探讨了Dll4/Notch通路通过eprhinB2对滋养细胞生物学效应的影响；以蜕膜NK细胞为主要研究对象，揭示了其在妊娠早期通过分泌炎性细胞因子影响血管平滑肌细胞功能，启动子宫螺旋动脉重铸过程；以外泌体介导母胎界面信息沟通交流为切入点，发现滋养细胞来源的外泌体调节蜕膜NK细胞分泌功能。同时受本项目资助，对子痫前期胎盘来源外泌体对血管功能障碍进行了初步研究，证实子痫前期胎盘来源的外泌体包含的miRNA可以介导血管平滑肌细胞生物学功能。上述成果已发表SCI论文3篇，已接收SCI论文1篇，在投SCI论文2篇。