山西医科大学学报2026,Vol.57Issue(7):750-758,9.DOI:10.13753/j.issn.1007-6611.2026.07.003
基于蛋白质组学解析PMA与TCM诱导中性粒细胞胞外捕获网的蛋白组分及分子通路差异
Differences in protein components and molecular pathways of neutrophil extracellular traps induced by PMA and TCM based on proteomics
摘要
Abstract
Objective To compare the differences and similarities of neutrophil extracellular traps(NETs)under various induction conditions based on proteomic techniques,and elucidate their core common mechanisms and specific regulatory pathways for providing experimental evidence in the precise targeting of tumor-associated NETs.Methods Bone marrow neutrophils were isolated from BALB/c mice and induced to form NETs using phorbol 12-myristate 13-acetate(PMA)or tumor cell-conditioned medium(TCM).NETs were verified by immunofluorescence staining.Protein expression profiles were detected using untargeted quantitative proteomics.Bioinformatics analyses were performed to assess the subcellular localization,Gene Ontology(GO)functional enrichment,Kyoto Ency-clopedia of Genes and Genomes(KEGG)pathway enrichment and protein-protein interaction network analysis of common proteins and differential proteins.Results Both PMA and TCM successfully induced NETs.A total of 8 966 common proteins were identified in both two groups,including classical NET markers such as histone,neutrophil elastase(NE),and myeloperoxidase(MPO).These proteins were primarily localized in the cytoplasm and cell membrane,and involved in basic metabolism,substance transport,and structural assembly.A total of 2 765 differential proteins were identified between the two groups.Proteins up-regulated in PMA-induced NETs were enriched in oxidative phosphorylation,reactive oxygen species production,and phagosome pathways.Proteins up-regulated in TCM-induced NETs were enriched in cell cycle regulation,DNA repair,metabolic reprogramming,complement-coagulation cascades,and tumor-associated inflammatory pathways.Conclusion PMA-and TCM-induced NETs share conserved core proteins and basic pathways while exhibiting significant stimulus-specific features,presenting a"conserved yet distinct"profile.TCM-induced NETs tend to develop an adaptive phenotype tailored to the tumor microenvironment.This study provides a theoretical basis for distinguishing the molecular characteristics of classical chemical-induced NETs from tumor-associated NETs and developing targeted therapeutic strategies.关键词
中性粒细胞胞外捕获网/肿瘤上清/肿瘤微环境/佛波酯/蛋白质组学/NETosisKey words
neutrophil extracellular traps/tumor cell culture supernatant/tumor microenvironment/phorbol 12-myristate 13-acetate/proteomics/NETosis分类
医药卫生引用本文复制引用
张春丽,杜轲,黄立敏,慕艳华,贺改霞..基于蛋白质组学解析PMA与TCM诱导中性粒细胞胞外捕获网的蛋白组分及分子通路差异[J].山西医科大学学报,2026,57(7):750-758,9.基金项目
陕西省自然科学基础研究计划项目(2019JQ-962) (2019JQ-962)
西安交大基础临床融合项目(YXJLRH2022098) (YXJLRH2022098)
西安交大二附院自由探索项目[2020YJ(ZYTS)546-03] (ZYTS)