人参皂苷Rb1 预处理间充质干细胞的转录组分析及急性肾损伤治疗关键基因挖掘  

Transcriptome analysis of mesenchymal stem cells pretreated with ginsenoside Rb1 and mining of key genes for treating acute kidney injury

作　　者：张可颖 冀雨薇 付章宁 张益帆 王晓晨[1] 杨滟 陈香美[1] 蔡广研[1] 洪权[1] Keying Zhang;Yuwei Ji;Zhangning Fu;Yifan Zhang;Xiaochen Wang;Yan Yang;Xiangmei Chen;Guangyan Cai;Quan Hong(Department of Nephrology,First Medical Center of Chinese PLA General Hospital,State Key Laboratory of Kidney Diseases,National Clinical Research Center for Kidney Diseases,Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases,Beijing Key Laboratory of Digital Intelligent TCM for Prevention and Treatment of Pan-vascular Diseases,Key Disciplines of National Administration of Traditional Chinese Medicine(zyyzdxk-2023310);Chinese PLA Medical College,Beijing 100853,China)

机构地区：[1]解放军总医院第一医学中心肾脏病医学部、肾脏疾病全国重点实验室、国家慢性肾病临床医学研究中心、重症肾脏疾病器械与中西医药物研发北京市重点实验室、数智中医泛血管疾病防治北京市重点实验室、国家中医药管理局高水平中医药重点学科,北京100853 [2]解放军医学院,北京100853

出　　处：《中华肾病研究电子杂志》2025年第1期26-33,共8页Chinese Journal of Kidney Disease Investigation(Electronic Edition)

基　　金：国家自然科学基金项目(82070741,82270758)。

摘　　要：目的本研究借助转录组学测序与生物信息学手段,深入分析人参皂苷Rb1处理间充质干细胞(MSCs)的差异表达基因(DEGs),旨在挖掘对急性肾损伤(AKI)具备潜在干预作用的关键基因,为AKI的治疗开辟新路径。方法本研究利用R4.4.2软件对GSE207667数据集进行分析,筛选人参皂苷Rb1处理MSCs后的DEGs。进一步通过基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,筛选与AKI相关的关键基因;并通过功能注释,结合文献回顾和数据库分析,对筛选出的关键基因进行深入探讨。结果从人参皂苷Rb1处理的MSCs中,共鉴定出2969个DEGs,其中上调基因1567个,下调基因1402个(|log2FC|>0.585)。GO富集分析显示,这些DEGs主要富集于生物功能和分子功能,涉及细胞群增殖和凋亡细胞清除的正向调节等生物功能。KEGG分析表明,DEGs在细胞因子-细胞因子受体相互作用、IL-17信号通路、铁死亡、细胞衰老和胞葬作用等通路中显著富集。基于功能注释结果,本研究挖掘到43个与AKI干预相关的潜在关键基因,并重点讨论了其中的骨形态发生蛋白2(BMP2)、基质金属蛋白酶13(MMP13)、自噬相关蛋白5(ATG5)、多效细胞蛋白(PTN)和神经生长因子(NGF)基因。这些基因在细胞增殖、细胞凋亡、炎症反应和组织修复等生物学过程发挥重要作用,可能与人参皂苷Rb1预处理MSCs干预AKI的机制密切相关。结论人参皂苷Rb1通过调控MSCs中的细胞增殖、细胞凋亡等生物学过程,可能对AKI发挥干预作用。本研究鉴定的5个关键基因(BMP2、MMP13、ATG5、PTN和NGF)为人参皂苷Rb1处理MSCs在AKI治疗中的应用提供了潜在靶点。Objective This study employed transcriptomic sequencing and bioinformatics analyses to identify differentially expressed genes(DEGs)in mesenchymal stem cells(MSCs)treated with ginsenoside Rb1,in order to uncover key genes with potential therapeutic effects on acute kidney injury(AKI),thereby providing novel insights for AKI treatment.Methods In this study,R4.4.2 software was employed to analyze the GSE207667 dataset for identifying DEGs in MSCs after ginsenoside Rb1 treatment.AKI-related key genes were then selected via Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The selected key genes were further examined through functional annotations,literature review,and database analysis.Results From the MSCs treated with ginsenoside Rb1,2969 DEGs were identified,comprising 1567 upregulated genes and 1402 downregulated genes(|log2FC|>0.585).GO enrichment analysis revealed that these DEGs were primarily about biological and molecular functions,including the positive regulation of cell population proliferation and apoptotic cell clearance.KEGG analysis further indicated significant enrichment of DEGs in pathways of cytokine-cytokine receptor interaction,IL-17 signaling,ferroptosis,cell senescence,and efferocytosis(P<0.05).Based on functional annotations,this study identified 43 potential key genes related to AKI intervention,and discussed focusing on genes of BMP2,MMP13,ATG5,PTN,and NGF.These genes were implicated in critical biological processes as cell proliferation,apoptosis,inflammation,and tissue repair,and may be closely linked to the mechanism in which MSCs pretreated by ginsenoside Rb1 modulated AKI.Conclusion Ginsenoside Rb1 may exert therapeutic effects on AKI by modulating biological processes of cell proliferation and apoptosis in MSCs.The five key genes identified in this study(BMP2,MMP13,ATG5,PTN,and NGF)may offer potential targets for the application of ginsenoside Rb1-treated MSCs in AKI therapy.

关 键 词：急性肾损伤 RNA 测序 网络药理学 间充质干细胞 人参皂苷RB1 

分 类 号：R28[医药卫生—中药学]