Abstract：
Preeclampsia (PE) is a pregnancy complication that encompasses various pathogenic mechanisms. Shallow implantation of the placenta due to abnormal trophoblast behavior is considered an important mechanism underlying PE; however, its exact etiology remains unclear.
The expression of OLFML3 in the placenta and important clinical indicators were performed, followed by a correlation analysis. The effect of OLFML3 on the behavior of HTR-8/SVneo cells was examined, and the downstream molecular mechanisms of OLFML3 were investigated in HTR-8/SVneo cells. Additionally, a rat model of PE was generated by adenovirus injection via the tail vein to verify the role of OLFML3.
OLFML3 is highly expressed in both syncytiotrophoblasts and cytotrophoblasts and deregulated in preeclamptic placentas. OLFML3 overexpression in HTR-8/SVneo cells promoted cell proliferation, migration, invasion, and impeded apoptosis, and triggered phosphorylation on ser473 of AKT. Conversely, OLFML3 knockdown exerted opposite effects. Furthermore, OLFML3 overexpression ameliorates CoCl2-induced apoptosis of HTR-8/SVneo cells. In a rat model, OLFML3 overexpression alleviates PE-associated maternal symptoms, leading to lower blood pressure, less severe proteinuria, improved fetal growth restriction, as well as upregulation of P-AKT and downregulation of Cleaved caspase3 and Bax.
OLFML3 may alleviate PE development by inhibiting extravillous trophoblast cell apoptosis through the PI3K/AKT pathway. Our findings indicated that OLFML3 may provide a possible therapeutic target for PE.
The expression of OLFML3 in the placenta and important clinical indicators were performed, followed by a correlation analysis. The effect of OLFML3 on the behavior of HTR-8/SVneo cells was examined, and the downstream molecular mechanisms of OLFML3 were investigated in HTR-8/SVneo cells. Additionally, a rat model of PE was generated by adenovirus injection via the tail vein to verify the role of OLFML3.
OLFML3 is highly expressed in both syncytiotrophoblasts and cytotrophoblasts and deregulated in preeclamptic placentas. OLFML3 overexpression in HTR-8/SVneo cells promoted cell proliferation, migration, invasion, and impeded apoptosis, and triggered phosphorylation on ser473 of AKT. Conversely, OLFML3 knockdown exerted opposite effects. Furthermore, OLFML3 overexpression ameliorates CoCl2-induced apoptosis of HTR-8/SVneo cells. In a rat model, OLFML3 overexpression alleviates PE-associated maternal symptoms, leading to lower blood pressure, less severe proteinuria, improved fetal growth restriction, as well as upregulation of P-AKT and downregulation of Cleaved caspase3 and Bax.
OLFML3 may alleviate PE development by inhibiting extravillous trophoblast cell apoptosis through the PI3K/AKT pathway. Our findings indicated that OLFML3 may provide a possible therapeutic target for PE.
摘要：
背景：先兆子痫（PE）是一种妊娠并发症，包括各种致病机制。由于滋养细胞异常行为导致的浅胎盘植入被认为是PE的重要机制;然而，其确切病因尚不清楚。
方法：对OLFML3在胎盘中的表达及重要临床指标进行检测，然后进行相关分析。检查了OLFML3对HTR-8/SVneo细胞行为的影响，并在HTR-8/SVneo细胞中研究了OLFML3的下游分子机制。此外,通过尾静脉注射腺病毒制备PE大鼠模型，以验证OLFML3的作用。
结果：OLFML3在合胞体滋养层和细胞滋养层中高表达，在先兆子痫胎盘中失调。OLFML3在HTR-8/SVneo细胞中的过表达促进细胞增殖，迁移,入侵,并阻碍了细胞凋亡，并在AKT的ser473上触发磷酸化。相反，OLFML3敲低产生相反的效果。此外，OLFML3过表达改善CoCl2诱导的HTR-8/SVneo细胞凋亡。在大鼠模型中,OLFML3过表达减轻PE相关的母体症状，导致血压降低，较不严重的蛋白尿，改善胎儿生长受限，以及P-AKT的上调和caspase3和Bax的下调。
结论：OLFML3可能通过PI3K/AKT通路抑制绒毛外滋养层细胞凋亡，从而减轻PE的发生。我们的发现表明OLFML3可能为PE提供可能的治疗靶标。
方法：对OLFML3在胎盘中的表达及重要临床指标进行检测，然后进行相关分析。检查了OLFML3对HTR-8/SVneo细胞行为的影响，并在HTR-8/SVneo细胞中研究了OLFML3的下游分子机制。此外,通过尾静脉注射腺病毒制备PE大鼠模型，以验证OLFML3的作用。
结果：OLFML3在合胞体滋养层和细胞滋养层中高表达，在先兆子痫胎盘中失调。OLFML3在HTR-8/SVneo细胞中的过表达促进细胞增殖，迁移,入侵,并阻碍了细胞凋亡，并在AKT的ser473上触发磷酸化。相反，OLFML3敲低产生相反的效果。此外，OLFML3过表达改善CoCl2诱导的HTR-8/SVneo细胞凋亡。在大鼠模型中,OLFML3过表达减轻PE相关的母体症状，导致血压降低，较不严重的蛋白尿，改善胎儿生长受限，以及P-AKT的上调和caspase3和Bax的下调。
结论：OLFML3可能通过PI3K/AKT通路抑制绒毛外滋养层细胞凋亡，从而减轻PE的发生。我们的发现表明OLFML3可能为PE提供可能的治疗靶标。
