PGE2/SYT2介导细胞焦亡调控子宫内膜间质细胞迁移的机制研究

子宫内膜异位症（Endometriosis，EMs）是妇科常见病。异位在盆腔的子宫内膜组织和细胞诱发的炎症反应，是EMs发生发展的关键。课题组前期研究发现：EMs患者腹腔液中炎症因子前列腺素2（ProstaglandinE2,PGE2）升高，高浓度的PGE2通过上调SYT2基因诱导人子宫内膜间质细胞hEM15A发生焦亡，促进其迁移；但分子机制尚不清楚，本项目拟从以下4点研究：①研究PGE2/SYT2介导的细胞焦亡诱发子宫内膜间质细胞hEM15A迁移的特征；②研究PGE2/SYT2介导的细胞焦亡后，IL-1β和IL-18对子宫内膜间质细胞hEM15A迁移及炎症介质HMGB1蛋白表达的影响；③沉默HMGB1基因后，PGE2/SYT2介导的细胞焦亡对子宫内膜间质细胞hEM15A迁移力的影响；④建立EMs可视化裸鼠模型，体内验证PGE2/SYT2/HMGB1介导EMs进展的作用。

Endometriosis (EMs) is a common gynecological disease.The inflammation induced by ectopic endometrial cells in the pelvic cavity plays a vital role in EMs’ progression. The previous study found that: Prostaglandin E2 (PGE2) was increased in the peritoneal fluid of EMs patients. Also, high concentration of PGE2 induced the human endometrial stromal cell (hEM15A) pyroptosis through SYT2 gene, which promoted hEM15A’s migration. However, the mechanism is still unclear. This project will research the following four aspects: (1) To study the effect of PGE2/SYT2-induced pyroptosis on hEM15A’s migration;(2)After PGE2/SYT2-induced pyroptosis in hEM15A, researching the effect of IL-1β and IL-18 on hEM15A’s migration and the protein expression of HMGB1;(3)Knocking down HMGB1, identifying the effects of the migration in hEM15A induced by PGE2/SYT2; (4) EMs visualized nude mouse model was established to verify the PGE2/ SYT2-induced pyroptosis and HMGB1 expression in vivo, and to clarify the role of PGE2/SYT2-induced pyroptosis promoting the occurrence and development of EMs through HMGB1.