中国病理生理杂志2025,Vol.41Issue(6):1134-1144,11.DOI:10.3969/j.issn.1000-4718.2025.00.015
NETs通过调控细胞骨架和黏着斑形成抑制子痫前期胎盘中滋养细胞的迁移
Neutrophil extracellular traps suppress trophoblast migration in pre-eclamptic placenta through modulating cytoskeleton and focal adhesion formation
摘要
Abstract
AIM:To investigate the potential mechanism of neutrophil extracellular traps(NETs)in the pla-centa during the pathogenesis of preeclampsia(PE).METHODS:Differential neutrophil infiltration in PE versus normo-tensive placentas was assessed using placental transcriptome sequencing data.Single-cell sequencing analysis of GSE173193 dataset was conducted to evaluate the expression of NETs formation-related genes in neutrophils from PE pla-centa and control placenta.Immunofluorescence and ELISA were used to measure NETs levels in placental tissues.Fol-lowing NETs generation and treatment of human extravillous trophoblast(EVT)HTR8/Svneo strain with NETs,RNA se-quencing was utilized to identify potential signaling pathways through which NETs regulate trophoblast function.RE-SULTS:Neutrophil infiltration,and expression of NETs formation critical genes,MPO(myeloperoxidase)and ELANE(elastase,neutrophil expressed),in neutrophils were significantly increased in PE placentas compared with controls.The level of NETs was elevated in PE placentas as well.The NETs significantly inhibited the migration of HTR8/Svneo cells.Disrupted F-actin arrangement,aggregate formation,and reduced paxillin expression were observed in NETs-treated HTR8/Svneo cells.Single-cell sequencing analysis revealed that focal adhesion and stress fiber pathways were down-regu-lated in the EVT of PE placenta.CONCLUSION:Neutrophil infiltration and NETs formation were increased in PE.The NETs may inhibit EVT migration by inducing stress fiber disassembly and down-regulating paxillin expression,thereby dis-rupting cytoskeletal organization and focal adhesion formation.关键词
子痫前期/中性粒细胞细胞外诱捕网/滋养细胞/细胞迁移/应力纤维/黏着斑Key words
preeclampsia/neutrophil extracellular traps/trophoblast/cell migration/stress fiber/focal adhesion分类
医药卫生引用本文复制引用
叶迅伽,庸安露,庾洁盈,鲁馨瑶,李瑞满,杨雪松,宛硕,王广..NETs通过调控细胞骨架和黏着斑形成抑制子痫前期胎盘中滋养细胞的迁移[J].中国病理生理杂志,2025,41(6):1134-1144,11.基金项目
国家自然科学基金资助项目(No.82371692) (No.82371692)