[1]冀 伟,郭 倩,郑广涛,等.GPER抑制IGF2R表达介导缺血性脑卒中的抗炎作用[J].陕西医学杂志,2023,52(4):369-375.[doi:DOI:10.3969/j.issn.1000-7377.2023.04.002]
　JI Wei,GUO Qian,ZHENG Guangtao,et al.GPER mediates anti-inflammatory effect of ischemic stroke by inhibiting expression of IGF2R[J].,2023,52(4):369-375.[doi:DOI:10.3969/j.issn.1000-7377.2023.04.002]
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GPER抑制IGF2R表达介导缺血性脑卒中的抗炎作用
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
52
期数:
2023年4期
页码:
369-375
栏目:
基础研究
出版日期:
2023-04-05

文章信息/Info

Title:
GPER mediates anti-inflammatory effect of ischemic stroke by inhibiting expression of IGF2R
作者:
冀 伟; 郭 倩; 郑广涛; 寇巧春; 王 磊
(新疆医科大学第五附属医院,新疆 乌鲁木齐 830000)
Author(s):
JI Wei; GUO Qian; ZHENG Guangtao; KOU Qiaochun; WANG Lei
(The Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)
关键词:
缺血性脑卒中;  生物信息学;  免疫;  G蛋白偶联受体家族;  胰岛素样生长因子2受体;  中性粒细胞
Keywords:
Ischemic stroke;  Bioinformatics;  Immunity;  GPER;  IGF2R;  Neutrophils
分类号:
R 743
DOI:
DOI:10.3969/j.issn.1000-7377.2023.04.002
文献标志码:
A
摘要:
目的:探讨缺血性脑卒中(IS)的潜在治疗靶标及分子机制。方法:识别GSE16561和GSE22255数据中IS和对照之间的差异表达基因中的免疫相关基因,并进行富集分析。利用随机森林算法对基因进行重要性排序,并评价核心基因的诊断能力。鉴定IS中免疫细胞水平并与核心基因进行相关性分析。在IS和对照的外周血样本中验证关键基因和免疫细胞的水平。此外,在建立的大鼠IS模型中评价G蛋白偶联受体家族(GPER)的治疗作用及调控机制。结果:共鉴定了59个免疫相关的差异表达基因,显著参与MAPK信号通路、PI3K-Akt信号通路。选择重要性排序前10的基因作为核心基因,并发现胰岛素样生长因子2受体(IGF2R)的诊断能力最高。IGF2R与中性粒细胞的相关性最大。分子实验验证了IGF2R和中性粒细胞在IS患者中显著升高。GPER治疗明显改善了大鼠缺血性脑卒中,并降低了模型大鼠中IGF2R的表达。结论:GPER对IS的治疗作用可能与降低IGF2R的表达有关。
Abstract:
Objective:To explore the potential therapeutic targets and molecular mechanisms of ischemic stroke.Methods:Immune related genes among differentially expressed genes between ischemic stroke(IS)and controls in the GSE16561 and GSE22255 data were identified and subjected to enrichment analysis.A random forest algorithm was used to rank genes by importance and evaluate the diagnostic ability of core genes.The level of immune cells in IS was identified and the correlation between immune cells and core genes was analyzed.Levels of genes and immune cells were verified in peripheral blood samples of IS and controls.In addition,the therapeutic effects and regulatory mechanisms of family of G protein coupled receptors(GPER)were evaluated in established rat IS model.Results:A total of 59 immune related differentially expressed genes were identified,which were significantly involved in the MAPK signaling pathway,PI3K-Akt signaling pathway.The top 10 genes from the importance ranking were selected as core genes and insulin like growth factor 2 receptor(IGF2R)was found to have the highest diagnostic ability.IGF2R was most associated with neutrophils.Molecular experiments validated that IGF2R and neutrophils were significantly elevated in IS patients.GPER treatment clearly ameliorated cerebral infarction in model rats and reduced IGF2R expression.Conclusion:The therapeutic effect of GPER on IS may be associated with reducing the expression of IGF2R.

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备注/Memo

备注/Memo:
基金项目:新疆维吾尔自治区卫生健康委员会青年医学科技人才专项课题(WJWY-201918)
更新日期/Last Update: 2023-04-06