军事医学2025，Vol.49Issue(10)：721-727,7.DOI:10.7644/j.issn.1674-9960.2025.10.001
钙卫蛋白S100A8/A9对原代小鼠肝星状细胞激活效应的定量蛋白质组学研究
Effects of calprotectin S100A8/A9 on primary hepatic stellate cells of mice based on quantitative proteomics
摘要
Abstract
Objective To investigate the direct stimulatory effects of calprotectin S100A8/A9 on hepatic stellate cells(HSCs)and underlying regulatory mechanisms.Methods Primary HSCs of mice were stimulated with S100A8/A9 heterodimer recombinant protein at 200 and 1000 ng/mL.Data on quantitative proteomics was obtained using the tandem mass tag(TMT)-labeled method before changes in the protein level of HSCs were analyzed.Differentially expressed proteins(DEPs)were screened using Significance B method and P＜0.05,followed by Reactome pathway enrichment analysis.Furthermore,protein-protein interactions between the DEPs enriched in the pathways were analyzed using the STRING database.Results The protein expression profile of HSCs was significantly altered after treatment with S100A8/A9 at 1000 ng/mL.Reactome pathway enrichment analysis revealed significant enrichment in such pathways as transforming growth factor-beta(TGF-β)signaling,nuclear factor kappa-B(NF-κB)signaling activation,cytokine-mediated immune regulation,and collagen biosynthesis.The analysis of protein-protein interactions identified NF-kappa-B transcription factor subunit(RELB),chemokine(C-X-C motif)ligand 10(CXCL10)and Notch receptor 1(NOTCH1)as key hub proteins in the regulatory network.Conclusion S100A8/A9 can directly stimulate the activation of HSCs,through NF-κB signaling,TGF-β signaling,and Notch signaling pathways potentially.This study sheds light on the mechanisms underlying the activation of HSCs stimulated by S100A8/A9.关键词
钙卫蛋白S100A8/A9/肝星状细胞/定量蛋白质组学/肝纤维化Key words
calprotectin S100A8/A9/hepatic stellate cells/quantitative proteomics/liver fibrosis分类
临床医学引用本文复制引用
刘睿茜,刘金芳,王建,徐平..钙卫蛋白S100A8/A9对原代小鼠肝星状细胞激活效应的定量蛋白质组学研究[J].军事医学,2025,49(10):721-727,7.基金项目
国家自然科学基金项目(32141003,32371503) （32141003,32371503）
国家重点研发计划(2024YFC3405400) （2024YFC3405400）
北京市自然科学基金-大兴创新联合基金(L246037) （L246037）
医学蛋白质组学全国重点实验室项目(SKLP-K202201) （SKLP-K202201）
