下调的 ETV4 抑制子痫前期滋养细胞的增殖、迁移和侵袭。
Downregulated ETV4 inhibits the proliferation, migration, and invasion of trophoblast cells in preeclampsia.
机构信息
Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China.
Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China.
出版信息
Reproduction. 2023 Mar 8;165(4):373-381. doi: 10.1530/REP-22-0184. Print 2023 Apr 1.
IN BRIEF
Preeclampsia is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes, but the mechanisms underlying the development of preeclampsia are not fully understood. This study shows that ETV4 plays an essential role in the proliferation, invasion, and migration of trophoblast cells by regulating MMP-2 and MMP-9 and is involved in the pathogenesis of preeclampsia.
ABSTRACT
Preeclampsia (PE) is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes. However, the mechanisms underlying the development of PE are not fully understood. ETS Variant Transcription Factor 4 (ETV4) plays an important role in cell proliferation, migration, and invasion. In this study, we aimed to explore the potential function of ETV4 in placental trophoblast cells. We analyzed the expression and location of ETV4 in PE and uncomplicated placental tissues using RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence staining. The results showed that both the mRNA and protein levels of ETV4 were markedly decreased in PE placental tissues compared with placental tissues from women with uncomplicated pregnancies (P < 0.05). Then, the effects of ETV4 on HTR-8/SVneo and Bewo cell proliferation, migration, and invasion were evaluated by MTT, 5-ethynyl-2-deoxyuridine (EdU), wound healing, and Transwell assays, respectively. The results showed that ETV4 knockdown inhibited both HTR-8/SVneo and Bewo cell proliferation, migration, and invasion (P < 0.05). Conversely, overexpression of ETV4 promoted both HTR-8/SVneo and Bewo cell proliferation, migration, and invasion (P < 0.05). We then measured the expression of MMP-2 and MMP-9 in HTR8/SVneo cells. We found that ETV4 knockdown decreased the mRNA and protein expression of MMP-2 and MMP-9, while ETV4 overexpression increased MMP-2 and MMP-9 mRNA and protein expression (P < 0.05). In conclusion, ETV4 plays an essential role in the proliferation, invasion, and migration of trophoblast cells by regulating MMP-2 and MMP-9. Our findings provide novel insight into the mechanisms underlying the occurrence of PE.
摘要
子痫前期（PE）是一种妊娠并发症，可导致严重的母婴不良结局。然而，PE 发展的机制尚不完全清楚。ETS 变异转录因子 4（ETV4）在细胞增殖、迁移和侵袭中发挥重要作用。在这项研究中，我们旨在探讨 ETV4 在胎盘滋养层细胞中的潜在功能。我们使用 RT-qPCR、Western blot、免疫组织化学和免疫荧光染色分析了 PE 和无并发症胎盘组织中 ETV4 的表达和定位。结果表明，与无并发症妊娠的胎盘组织相比，PE 胎盘组织中 ETV4 的 mRNA 和蛋白水平均明显降低（P < 0.05）。然后，通过 MTT、5-乙炔基-2-脱氧尿苷（EdU）、划痕愈合和 Transwell 测定分别评估了 ETV4 对 HTR-8/SVneo 和 Bewo 细胞增殖、迁移和侵袭的影响。结果表明，ETV4 敲低抑制了 HTR-8/SVneo 和 Bewo 细胞的增殖、迁移和侵袭（P < 0.05）。相反，ETV4 的过表达促进了 HTR-8/SVneo 和 Bewo 细胞的增殖、迁移和侵袭（P < 0.05）。我们随后测量了 HTR8/SVneo 细胞中 MMP-2 和 MMP-9 的表达。我们发现，ETV4 敲低降低了 MMP-2 和 MMP-9 的 mRNA 和蛋白表达，而 ETV4 过表达增加了 MMP-2 和 MMP-9 的 mRNA 和蛋白表达（P < 0.05）。总之，ETV4 通过调节 MMP-2 和 MMP-9 在滋养层细胞的增殖、侵袭和迁移中发挥重要作用。我们的研究结果为 PE 发生的机制提供了新的见解。
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