Department of Obstetrics, Shenzhen People's Hospital (The Second Clinical Medical College, 47885Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China.
Department of Obstetrics, Shenzhen Baoan Women's and Children's Hospital, Shenzhen, China.
Cell Transplant. 2020 Jan-Dec;29:963689720965979. doi: 10.1177/0963689720965979.
Preeclampsia is a pregnancy disorder, whereas the underlying mechanisms and etiological factors of this complication remain elusive. Studies have reported that decreased invasiveness of trophoblast cells, immunity disorder in the maternal-fetal interface, and oxidative stress may contribute to the development of preeclampsia. In the present study, we firstly co-cultured the smooth muscle cells (SMCs) and endothelial cells (ECs) to mimic the decidua and myometrium interface and examined the effects of osteopontin (OPN) on the invasive potential of trophoblasts in the SMC-EC co-culturing system. Our results showed that HTR-8/SVneo cells after hypoxia treatment showed enhanced invasive potential in the SMC-EC co-culturing system. OPN levels in the culture media from hypoxia-treated HTR-8/SVneo cells were significantly increased. More importantly, OPN treatment upregulated integrin, beta 3 and integrin, beta 5 expression in HTR-8/SVneo cells, and promoted HTR-8/SVneo cell invasion in the transwell invasion assay and SMC-EC co-culturing system. Mechanistically, treatment with integrin αvβ3 inhibitor significantly attenuated the enhanced invasive potential of HTR-8/SVneo cells treated with OPN in the SMC-EC co-culturing system. In conclusion, our study for the first time established the SMC-EC co-culturing system to examine the invasive potential of trophoblasts. Our results indicated that OPN promoted the invasive capacity of trophoblasts via at least targeting αvβ3 in the EC-SMC co-culturing system. Future studies were required to further validate the EC-SMC co-culturing system and to determine the molecular mechanisms of OPN-mediated trophoblast invasion.
子痫前期是一种妊娠疾病，但其潜在机制和病因仍不清楚。研究表明，滋养细胞侵袭能力下降、母胎界面免疫紊乱和氧化应激可能导致子痫前期的发生。本研究首次通过共培养平滑肌细胞（SMCs）和内皮细胞（ECs）模拟蜕膜和子宫肌界面，探讨骨桥蛋白（OPN）对SMCs-EC 共培养体系中滋养细胞侵袭潜能的影响。结果显示，缺氧处理后的 HTR-8/SVneo 细胞在 SMC-EC 共培养体系中侵袭潜能增强，缺氧处理的 HTR-8/SVneo 细胞培养基中 OPN 水平显著升高。更重要的是，OPN 处理可上调 HTR-8/SVneo 细胞整合素β 3 和整合素β 5 的表达，并促进 HTR-8/SVneo 细胞在 Transwell 侵袭实验和 SMC-EC 共培养体系中的侵袭。机制研究表明，整合素αvβ3 抑制剂可显著抑制 OPN 处理后 HTR-8/SVneo 细胞在 SMC-EC 共培养体系中的侵袭潜能。综上所述，本研究首次建立了 SMC-EC 共培养体系来研究滋养细胞的侵袭潜能，结果表明 OPN 通过靶向 EC-SMC 共培养体系中的αvβ3 促进滋养细胞的侵袭能力。未来的研究需要进一步验证 EC-SMC 共培养体系，并确定 OPN 介导的滋养细胞侵袭的分子机制。
