分析蛛网膜下腔出血后 72 小时或假手术小鼠大脑中小鼠小神经胶质细胞中不同表达的 RNA 结合蛋白基因。
Analysis of different expression RNA binding protein genes in mouse microglia cell from the brains of mice 72 h after subarachnoid hemorrhage or sham operation.
机构信息
Jiangxi Medical College, Huan kui Academy, Nanchang University, Nanchang, Jiangxi, P.R. China.
Department of Neurosurgery, The first affiliated hospital,Jiangxi Medical college,Nanchang University, Nanchang, Jiangxi, China.
出版信息
BMC Med Genomics. 2024 Aug 2;17(1):194. doi: 10.1186/s12920-024-01972-x.
BACKGROUND
The prognosis of brain injury caused by subarachnoid hemorrhage (SAH) is poor. Previous studies showed that abnormal function of RBPs might be involved in brain injury, neuroinflammation and further affect microglia homeostasis. However, no studies have systematically analyzed the genome-wide abnormal expression of RBPs genes in microglia during SAH.
METHODS
RNA-seq data of microglia from the SAH mouse group (SAH) and control sham-operated mouse group (sham) were downloaded from the GEO database in GSE167957, including four samples from the sham group and four samples from the SAH group for subsequent analysis.Utilizing GO and KEGG functional enrichment analyses, we conducted a comprehensive study of differentially expressed genes (DEGs), alternative splicing patterns, and co-expression networks to gain deeper insights into the differential expression of RNA-binding proteins (RBPs) and differential alternative splicing events (ASEs) between the SAH (subarachnoid hemorrhage) and sham groups. This analysis aimed to elucidate the potential mechanisms underlying the aberrant expression of RBPs in microglia during brain injury caused by SAH.
RESULTS
ASEs and co-expression analyses of differentially expressed RBPs and differential ASEs were carried out in microglia in terms of gene expression. GO and KEGG functional enrichment analysis showed that aberrantly expressed RBPs such as Mcm7, Mtdh, SRSF3, and Hnrnpa2b1 may affect and regulate downstream Csnk1d, Uckl1 and other protein phosphorylation-related genes by alterative splicing.
CONCLUSION
RBPs were aberrantly expressed in microglia during the development of brain injury secondary to SAH, regulating alterative splicing of downstream genes and influencing the progression of SAH brain injury in this study. This implies that RBPs are important for the identification of new therapeutic targets for brain injury after SAH.
背景
蛛网膜下腔出血（SAH）引起的脑损伤预后较差。既往研究表明，RBP 异常功能可能参与脑损伤、神经炎症，并进一步影响小胶质细胞稳态。然而，目前尚无研究系统分析过 SAH 中小胶质细胞中 RBP 基因的全基因组异常表达。
方法
从 GEO 数据库的 GSE167957 中下载 SAH 小鼠组（SAH）和对照假手术组（sham）的小胶质细胞 RNA-seq 数据，包括 sham 组 4 个样本和 SAH 组 4 个样本，用于后续分析。利用 GO 和 KEGG 功能富集分析，我们对差异表达基因（DEGs）、可变剪接模式和共表达网络进行了全面研究，以深入了解 SAH 和 sham 组之间 RNA 结合蛋白（RBP）的差异表达和差异可变剪接事件（ASE）。该分析旨在阐明在 SAH 引起的脑损伤中小胶质细胞中 RBP 异常表达的潜在机制。
结果
对小胶质细胞中差异表达的 RBP 和差异 ASE 进行了基因表达的 ASE 和共表达分析。GO 和 KEGG 功能富集分析表明，Mcm7、Mtdh、SRSF3 和 Hnrnpa2b1 等异常表达的 RBP 可能通过可变剪接影响和调节下游 Csnk1d、Uckl1 等蛋白磷酸化相关基因。
结论
在 SAH 继发脑损伤的发展过程中，RBP 在小胶质细胞中异常表达，调节下游基因的可变剪接，并影响 SAH 脑损伤的进展。这表明 RBP 是识别 SAH 后脑损伤新治疗靶点的重要因素。
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