Department of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu Province, 215006, China.
Beijing Neurosurgical Institute & Department of Neurosurgery, Beijing Tiantan Hospital Affiliated to Capital Medical University, Capital Medical University, Beijing, China.
Inflammation. 2023 Aug;46(4):1290-1304. doi: 10.1007/s10753-023-01807-4. Epub 2023 Mar 20.
Inflammatory responses after intracerebral hemorrhage (ICH) contribute to severe secondary brain injury, leading to poor clinical outcomes. However, the responsible genes for effective anti-inflammation treatment in ICH remain poorly elucidated. The differentially expressed genes (DEGs) of human ICH were explored by online GEO2R. Go and KEGG were used to explore the biological function of DEGs. Protein-protein interactions (PPI) were built in the String database. Critical modules of PPI were identified by a molecular complex detection algorithm (MCODE). Cytohubba was used to determine the hub genes. The mRNA-miRNA interaction network was built in the miRWalk database. The rat ICH model was applied to validate the key genes. A total of 776 DEGs were identified in ICH. Go and KEGG analyses indicated that DEGs were mainly involved in neutrophil activation and the TNF signaling pathway. GSEA analysis presented that DEGs were significantly enriched in TNF signaling and inflammatory response. PPI network was constructed in the 48 differentially expressed inflammatory response-related genes. The critical module of the PPI network was constructed by 7 MCODE genes and functioned as the inflammatory response. The top 10 hub genes with the highest degrees were identified in the inflammatory response after ICH. CCL20 was confirmed as a key gene and mainly expressed in neurons in the rat ICH model. The regulatory network between CCL20 and miR-766 was built, and the miR-766 decrease was confirmed in a human ICH dataset. CCL20 is a key biomarker of inflammatory response after intracerebral hemorrhage, providing a potential target for inflammatory intervention in ICH.
脑出血（ICH）后的炎症反应导致严重的继发性脑损伤，导致临床预后不良。然而，ICH 有效抗炎治疗的相关基因仍未阐明。通过在线 GEO2R 探索人类 ICH 的差异表达基因（DEGs）。GO 和 KEGG 用于探索 DEGs 的生物学功能。在 String 数据库中构建蛋白质-蛋白质相互作用（PPI）。通过分子复合物检测算法（MCODE）识别 PPI 的关键模块。使用 Cytohubba 确定枢纽基因。在 miRWalk 数据库中构建 mRNA-miRNA 相互作用网络。应用大鼠 ICH 模型验证关键基因。在 ICH 中鉴定出 776 个 DEGs。GO 和 KEGG 分析表明，DEGs 主要参与中性粒细胞激活和 TNF 信号通路。GSEA 分析表明，DEGs 在 TNF 信号和炎症反应中显著富集。在 48 个差异表达的炎症反应相关基因中构建 PPI 网络。通过 7 个 MCODE 基因构建 PPI 网络的关键模块，并作为炎症反应发挥作用。鉴定出脑出血后炎症反应中具有最高度数的前 10 个枢纽基因。CCL20 被确认为关键基因，主要在大鼠 ICH 模型中的神经元中表达。构建了 CCL20 和 miR-766 之间的调控网络，并在人类 ICH 数据集确认了 miR-766 的降低。CCL20 是脑出血后炎症反应的关键生物标志物，为 ICH 中炎症干预提供了潜在的靶点。
