Neutrophil extracellular traps suppress trophoblast migration in pre-eclamptic placenta through modulating cytoskeleton and focal adhesion formation
10.3969/j.issn.1000-4718.2025.00.015
- VernacularTitle: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
- Author:
Xunjia YE
1
;
Anlu YONG
;
Jieying YU
;
Xinyao LU
;
Ruiman LI
;
Xue-song YANG
;
Shuo WAN
;
Guang WANG
Author Information
1. 暨南大学基础医学与公共卫生学院组织学与胚胎学系,广东 广州 510632;暨南大学基础医学与公共卫生学院病理生理学系,国家中医药管理局病理生理实验室,广东 广州 510632
- Publication Type:Journal Article
- Keywords:
preeclampsia;
neutrophil extracellular traps;
trophoblast;
cell migration;
stress fiber;
focal adhesion
- From:
Chinese Journal of Pathophysiology
2025;41(6):1134-1144
- CountryChina
- Language:Chinese
-
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.
