Cui Jie, Wang Hongbin, Liu Shiyao, Zhao Yiming
Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China.
National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People's Republic of China.
J Inflamm Res. 2024 Jan 18;17:399-415. doi: 10.2147/JIR.S438205. eCollection 2024.
Spontaneous intracerebral hemorrhage (ICH) is a subtype of stroke leading to high rates of morbidity and mortality in adults. Recent studies showed that immune and inflammatory responses might play essential roles in secondary brain injury. The purpose of this article was to provide a reference for further therapeutic strategies for ICH patients.
GSE206971 and GSE216607 datasets from the gene expression omnibus (GEO) database were used to screen the highly immune-related differentally expressed genes (IRDEGs). We used the CIBERSORT algorithm to assess the level of immune signatures infiltration and got the possible function of IRDEGs which was analyzed through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Protein-protein interaction (PPI) networks and six hub genes were identified in the Cytoscape plug-in. GSVA algorithm was performed to evaluate the potential pathways of six hub genes in ICH samples. The expression level of IL-7R chosen from six hub genes was further validated by Western blotting. The cell models of ICH were established for the research of IL-7/IL-7R signaling way.
A total of six hub genes (ITGAX, ITGAM, CCR2, CD28, SELL, and IL-7R) were identified. IL-7R was highly expressed in the mice ICH group, as shown by immunoblotting. Next, we constructed ICH cell models in RAW264.7 cells and BV2 cells. After treatment with IL-7, iNOS expression (M1 marker) was greatly inhibited while Arg-1(M2 marker) was enhanced, and it might function via the JAK3/STAT5 signaling pathway.
The hypothesis is proposed that the IL-7/IL-7R signaling pathway might regulate the inflammatory process following ICH by regulating microglia polarization. Our study is limited and requires more in-depth experimental confirmation.
自发性脑出血（ICH）是中风的一种亚型，可导致成人出现高发病率和死亡率。最近的研究表明，免疫和炎症反应可能在继发性脑损伤中起重要作用。本文旨在为ICH患者的进一步治疗策略提供参考。
使用来自基因表达综合数据库（GEO）的GSE206971和GSE216607数据集筛选高度免疫相关的差异表达基因（IRDEGs）。我们使用CIBERSORT算法评估免疫特征浸润水平，并通过基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）通路分析来分析IRDEGs的可能功能。在Cytoscape插件中识别蛋白质-蛋白质相互作用（PPI）网络和六个枢纽基因。使用GSVA算法评估六个枢纽基因在ICH样本中的潜在通路。通过蛋白质印迹进一步验证从六个枢纽基因中选择的IL-7R的表达水平。建立ICH细胞模型以研究IL-7/IL-7R信号通路。
共鉴定出六个枢纽基因（ITGAX、ITGAM、CCR2、CD28、SELL和IL-7R）。免疫印迹显示，IL-7R在小鼠ICH组中高表达。接下来，我们在RAW264.7细胞和BV2细胞中构建了ICH细胞模型。用IL-7处理后，诱导型一氧化氮合酶（iNOS）表达（M1标志物）受到极大抑制，而精氨酸酶-1（Arg-1，M2标志物）表达增强，其可能通过JAK3/STAT5信号通路发挥作用。
提出假说，即IL-7/IL-7R信号通路可能通过调节小胶质细胞极化来调节ICH后的炎症过程。我们的研究存在局限性，需要更深入的实验证实。
