Chen Yueh-Chung, Liao Chen-Chung, Shui Hao-Ai, Huang Pei-Hsuan, Shih Li-Jane
Department of Medicine, School of Medicine, National Defense Medical Center, Taipei 114201, Taiwan.
Division of Cardiology, Department of Internal Medicine, Taipei City Hospital, Renai Branch, Taipei 106243, Taiwan.
Proteomes. 2023 Oct 12;11(4):31. doi: 10.3390/proteomes11040031.
Trophoblast migration and invasion play crucial roles in placental development. However, the effects of (-)-epigallocatechin-3-gallate (EGCG) on trophoblast cell functions remain largely unexplored. In this study, we investigated the impact of EGCG on the survival of trophoblast cells and employed a proteomics analysis to evaluate its influence on trophoblast cell migration and invasion. Be-Wo trophoblast cells were treated with EGCG, and a zone closure assay was conducted to assess the cell migration and invasion. Subsequently, a proteomics analysis was performed on the treated and control groups, followed by a bioinformatics analysis to evaluate the affected biological pathways and protein networks. A quantitative real-time PCR and Western blot analysis were carried out to validate the proteomics findings. Our results showed that EGCG significantly suppressed the trophoblast migration and invasion at a concentration not affecting cell survival. The proteomics analysis revealed notable differences in the protein expression between the EGCG-treated and control groups. Specifically, EGCG downregulated the signaling pathways related to EIF2, mTOR, and estrogen response, as well as the processes associated with the cytoskeleton, extracellular matrix, and protein translation. Conversely, EGCG upregulated the pathways linked to lipid degradation and oxidative metabolism. The quantitative PCR showed that EGCG modulated protein expression by regulating gene transcription, and the Western blot analysis confirmed its impact on cytoskeleton and extracellular matrix reorganization. These findings suggest EGCG may inhibit trophoblast migration and invasion through multiple signaling pathways, highlighting the potential risks associated with consuming EGCG-containing products during pregnancy. Future research should investigate the impact of EGCG intake on maternal and fetal proteoforms.
滋养层细胞的迁移和侵袭在胎盘发育中起着至关重要的作用。然而，（-）-表没食子儿茶素-3-没食子酸酯（EGCG）对滋养层细胞功能的影响在很大程度上仍未得到探索。在本研究中，我们研究了EGCG对滋养层细胞存活的影响，并采用蛋白质组学分析来评估其对滋养层细胞迁移和侵袭的影响。用EGCG处理Be-Wo滋养层细胞，并进行划痕实验以评估细胞迁移和侵袭。随后，对处理组和对照组进行蛋白质组学分析，接着进行生物信息学分析以评估受影响的生物学途径和蛋白质网络。进行了定量实时PCR和蛋白质印迹分析以验证蛋白质组学的结果。我们的结果表明，EGCG在不影响细胞存活的浓度下显著抑制了滋养层细胞的迁移和侵袭。蛋白质组学分析揭示了EGCG处理组和对照组之间蛋白质表达的显著差异。具体而言，EGCG下调了与真核起始因子2（EIF2）、哺乳动物雷帕霉素靶蛋白（mTOR）和雌激素反应相关的信号通路，以及与细胞骨架、细胞外基质和蛋白质翻译相关的过程。相反，EGCG上调了与脂质降解和氧化代谢相关的途径。定量PCR表明EGCG通过调节基因转录来调节蛋白质表达，蛋白质印迹分析证实了其对细胞骨架和细胞外基质重组的影响。这些发现表明EGCG可能通过多种信号通路抑制滋养层细胞的迁移和侵袭，突出了孕期食用含EGCG产品的潜在风险。未来的研究应调查摄入EGCG对母体和胎儿蛋白质组型的影响。
