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中华肾病研究电子杂志 ›› 2025, Vol. 14 ›› Issue (01) : 26 -33. doi: 10.3877/cma.j.issn.2095-3216.2025.01.005

论著

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
张可颖1,2, 冀雨薇1,2, 付章宁1,2, 张益帆1, 王晓晨1, 杨滟1, 陈香美1, 蔡广研1, 洪权1,()   
  1. 1. 100853 北京,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
    2. 100853 北京,解放军医学院
  • 收稿日期:2025-01-24 出版日期:2025-02-28
  • 通信作者: 洪权
  • 基金资助:
    国家自然科学基金项目 (82070741,82270758)

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

Keying Zhang1,2, Yuwei Ji1,2, Zhangning Fu1,2, Yifan Zhang1, Xiaochen Wang1, Yan Yang1, Xiangmei Chen1, Guangyan Cai1, Quan Hong1,()   

  1. 1. 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)
    2. Chinese PLA Medical College; Beijing 100853, China
  • Received:2025-01-24 Published:2025-02-28
  • Corresponding author: Quan Hong
引用本文:

张可颖, 冀雨薇, 付章宁, 张益帆, 王晓晨, 杨滟, 陈香美, 蔡广研, 洪权. 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[J/OL]. 中华肾病研究电子杂志, 2025, 14(01): 26-33.

Keying Zhang, Yuwei Ji, Zhangning Fu, Yifan Zhang, Xiaochen Wang, Yan Yang, Xiangmei Chen, Guangyan Cai, Quan Hong. Transcriptome analysis of mesenchymal stem cells pretreated with ginsenoside Rb1 and mining of key genes for treating acute kidney injury[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2025, 14(01): 26-33.

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2 969 个DEGs,其中上调基因1 567 个,下调基因1 402 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.

图1 GSE207667 数据集差异表达基因的分析 注:FC:差异倍数;图示人参皂苷Rb1 处理间充质干细胞(MSCs)与无任何处理MSCs 间的差异表达基因,其中每个点代表一个基因,蓝色的点代表显著下调的基因,红色的点代表显著上调的基因,灰色的点就表示无显著差异的基因,两条垂直虚线为差异倍数线,一条水平虚线为显著水平线
图2 人参皂苷Rb1 增强间充质干细胞治疗作用潜在靶点的基因本体富集分析 注:A:基因本体富集分析中的生物过程气泡图;B:基因本体富集分析中的细胞组成气泡图;C:基因本体富集分析中的分子功能气泡图;基因比:该信号通路相关的基因数目与所有基因数目之比
图3 人参皂苷Rb1 增强间充质干细胞治疗作用潜在靶点的京都基因与基因组百科全书富集分析 注:基因比:该信号通路相关的基因数目与所有基因数目之比
表1 对急性肾损伤有治疗作用的差异表达基因筛选
富集分析 分组 信号通路 分子缩写 中文全称 Log2FC P 表达变化
KEGG - 细胞因子-细胞因子受体相互作用 TSLP 胸腺基质淋巴生成物 1. 07 0. 0413 上调
NGF 神经生长因子 0. 60 0. 0453 上调
BMP2 骨形态发生蛋白2 0. 61 0. 0006 上调
IL-17 信号通路 MMP13 基质金属蛋白酶 13 0. 59 0. 0019 上调
SRSF1 丝氨酸/ 精氨酸富集剪接因子 0. 61 0. 0025 上调
铁死亡 ACSL4 酰基辅酶a 合成酶长链家族成员4 0. 73 0. 0011 上调
ACSL3 酰基辅酶a 合成酶长链家族成员3 0. 63 0. 0035 上调
ATG5 自噬相关蛋白5 0. 68 0. 0004 上调
细胞衰老 PPP1CB 蛋白磷酸酶1 催化亚基 0. 63 0. 0189 上调
CCNE2 细胞周期蛋白E2 0. 61 0. 0006 上调
PPID 肽基脯氨酰异构酶 D 0. 69 0. 0015 上调
胞葬作用 CASP1 半胱天冬酶1 0. 82 0. 0405 上调
GULP1 含吞噬适配器的GULP PTB 结构域1 0. 84 0. 0269 上调
GO 生物过程 凋亡过程的正向调节 DDX3 DEAD-box 解旋酶3 0. 61  0. 0034  上调
PTN 多效生长因子 0. 62  0. 0247  上调
STK3 丝氨酸/ 苏氨酸激酶 0. 60  0. 0031  上调
CCAR1 细胞分裂周期与凋亡调控因子1 0. 61  0. 0006  上调
BMP2 骨形态发生蛋白2 0. 82  0. 0405  上调
CASP1 半胱天冬酶1 0. 60  0. 0029  上调
PMAIP1 PMA 诱导蛋白1 0. 69  0. 0015  上调
PPID 肽基脯氨酰异构酶D 1. 07  0. 0413  上调
细胞群增殖的正向调节 TSLP 胸腺基质淋巴生成素 0. 61  0. 0034  上调
PTN 多效生长因子 0. 60  0. 0453  上调
NGF 神经生长因子 0. 60  0. 0031  上调
CCAR1 细胞分裂周期与凋亡调控因子1 0. 69  0. 0013  上调
KITLG KIT 配体 0. 61  0. 0006  上调
BMP2 骨形态发生蛋白2 0. 68  0. 0219  上调
CNOT7 CCR4-NOT 转录复合体亚基7 0. 52  0. 0008  上调
RPS15A 核糖体蛋白S15A 0. 94  0. 0125  上调
EPCAM 上皮细胞粘附分子 0. 61  0. 0034 上调
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