PDF(Pubmed)
Abstract：
In this study, we investigate the effects of miRNA-138-5p and probable G-protein coupled receptor 124 (GPR124)-regulated inflammasome and downstream leukemia inhibitory factor (LIF)-STAT and adhesion molecule signaling in human decidual stromal cells. After informed consent was obtained from women aged 25-38 years undergoing surgical termination of the normal pregnancy and spontaneous miscarriage after 6-9 weeks of gestation, human decidual stromal cells were extracted from the decidual tissue. Extracellular vesicles (EVs) with microRNA (miRNA) between cells have been regarded as critical factors for embryo-maternal interactions on embryo implantation and programming of human pregnancy. MicroRNA-138-5p acts as the transcriptional regulator of GPR124 and the mediator of downstream inflammasome. LIF-regulated STAT activation and expression of integrins might influence embryo implantation. Hence, a better understanding of LIF-STAT and adhesion molecule signaling would elucidate the mechanism of microRNA-138-5p- and GPR124-regulated inflammasome activation on embryo implantation and pregnancy. Our results show that microRNA-138-5p, purified from the EVs of decidual stromal cells, inhibits the expression of GPR124 and the inflammasome, and activates the expression of LIF-STAT and adhesion molecules in human decidual stromal cells. Additionally, the knockdown of GPR124 and NLRP3 through siRNA increases the expression of LIF-STAT and adhesion molecules. The findings of this study help us gain a better understanding the role of EVs, microRNA-138-5p, GPR124, inflammasomes, LIF-STAT, and adhesion molecules in embryo implantation and programming of human pregnancy.
摘要：
在这项研究中,我们研究了microRNA-138-5p和GPR124调节人蜕膜基质细胞炎症小体和下游LIF-STAT和粘附分子信号传导的作用。在获得25-38岁女性的知情同意后，在妊娠6-9周后接受手术终止正常妊娠和自发性流产，从蜕膜组织中分离人蜕膜基质细胞。细胞间具有微小RNA(miRNA)的胞外囊泡已被认为是胚胎-母体相互作用对胚胎植入和人类妊娠编程的关键因素。MicroRNA-138-5p充当GPR124的转录调节因子和下游炎性体的介质。LIF调节的STAT激活和整合素的表达可能影响胚胎植入。因此，对LIF-STAT和粘附分子信号传导的更好理解将阐明microRNA-138-5p-和GPR124-调节炎症体激活对胚胎着床和妊娠的作用机制.我们的结果显示从蜕膜基质细胞纯化的细胞外囊泡，microRNA-138-5p抑制GPR124和炎性体表达，和microRNA-138-5p激活人蜕膜基质细胞中LIF-STAT和粘附分子的表达。此外,通过siRNA敲除GPR124和NLRP3增加了LIF-STAT和粘附分子的表达。我们的发现揭示了更好地理解细胞外囊泡的作用，microRNA-138-5p,GPR124,炎性体,和LIF-STAT和粘附分子在胚胎植入和人类妊娠编程中的作用。
