PDF(Pubmed)
Abstract：
BACKGROUND: Investigating immune cell infiltration in the brain post-ischemia-reperfusion (I/R) injury is crucial for understanding and managing the resultant inflammatory responses. This study aims to unravel the role of the RPS27A-mediated PSMD12/NF-κB axis in controlling immune cell infiltration in the context of cerebral I/R injury.
METHODS: To identify genes associated with cerebral I/R injury, high-throughput sequencing was employed. The potential downstream genes were further analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses. For experimental models, primary microglia and neurons were extracted from the cortical tissues of mouse brains. An in vitro cerebral I/R injury model was established in microglia using the oxygen-glucose deprivation/reoxygenation (OGD/R) technique. In vivo models involved inducing cerebral I/R injury in mice through the middle cerebral artery occlusion (MCAO) method. These models were used to assess neurological function, immune cell infiltration, and inflammatory factor release.
RESULTS: The study identified RPS27A as a key player in cerebral I/R injury, with PSMD12 likely acting as its downstream regulator. Silencing RPS27A in OGD/R-induced microglia decreased the release of inflammatory factors and reduced neuron apoptosis. Additionally, RPS27A silencing in cerebral cortex tissues mediated the PSMD12/NF-κB axis, resulting in decreased inflammatory factor release, reduced neutrophil infiltration, and improved cerebral injury outcomes in I/R-injured mice.
CONCLUSIONS: RPS27A regulates the expression of the PSMD12/NF-κB signaling axis, leading to the induction of inflammatory factors in microglial cells, promoting immune cell infiltration in brain tissue, and exacerbating brain damage in I/R mice. This study introduces novel insights and theoretical foundations for the treatment of nerve damage caused by I/R, suggesting that targeting the RPS27A and downstream PSMD12/NF-κB signaling axis for drug development could represent a new direction in I/R therapy.
METHODS: To identify genes associated with cerebral I/R injury, high-throughput sequencing was employed. The potential downstream genes were further analyzed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) analyses. For experimental models, primary microglia and neurons were extracted from the cortical tissues of mouse brains. An in vitro cerebral I/R injury model was established in microglia using the oxygen-glucose deprivation/reoxygenation (OGD/R) technique. In vivo models involved inducing cerebral I/R injury in mice through the middle cerebral artery occlusion (MCAO) method. These models were used to assess neurological function, immune cell infiltration, and inflammatory factor release.
RESULTS: The study identified RPS27A as a key player in cerebral I/R injury, with PSMD12 likely acting as its downstream regulator. Silencing RPS27A in OGD/R-induced microglia decreased the release of inflammatory factors and reduced neuron apoptosis. Additionally, RPS27A silencing in cerebral cortex tissues mediated the PSMD12/NF-κB axis, resulting in decreased inflammatory factor release, reduced neutrophil infiltration, and improved cerebral injury outcomes in I/R-injured mice.
CONCLUSIONS: RPS27A regulates the expression of the PSMD12/NF-κB signaling axis, leading to the induction of inflammatory factors in microglial cells, promoting immune cell infiltration in brain tissue, and exacerbating brain damage in I/R mice. This study introduces novel insights and theoretical foundations for the treatment of nerve damage caused by I/R, suggesting that targeting the RPS27A and downstream PSMD12/NF-κB signaling axis for drug development could represent a new direction in I/R therapy.
摘要：
背景：研究脑缺血再灌注（I/R）损伤后的免疫细胞浸润对于理解和管理由此产生的炎症反应至关重要。本研究旨在阐明RPS27A介导的PSMD12/NF-κB轴在脑I/R损伤背景下控制免疫细胞浸润中的作用。
方法：为了鉴定与脑I/R损伤相关的基因，采用高通量测序。使用基因本体论(GO)进一步分析了潜在的下游基因，京都基因和基因组百科全书（KEGG），和蛋白质-蛋白质相互作用(PPI)分析。对于实验模型，从小鼠大脑皮层组织中提取原代小胶质细胞和神经元。使用氧糖剥夺/复氧（OGD/R）技术在小胶质细胞中建立了体外脑I/R损伤模型。体内模型涉及通过大脑中动脉闭塞（MCAO）方法在小鼠中诱导脑I/R损伤。这些模型用于评估神经功能，免疫细胞浸润，和炎症因子释放。
结果：研究确定RPS27A是大脑I/R损伤的关键角色，PSMD12可能充当其下游监管机构。在OGD/R诱导的小胶质细胞中沉默RPS27A减少了炎症因子的释放并减少了神经元凋亡。此外,大脑皮层组织RPS27A沉默介导PSMD12/NF-κB轴,导致炎症因子释放减少，中性粒细胞浸润减少，并改善I/R损伤小鼠的脑损伤结果。
结论：RPS27A调节PSMD12/NF-κB信号轴的表达，导致小胶质细胞炎症因子的诱导，促进脑组织中的免疫细胞浸润，并加剧I/R小鼠的脑损伤。这项研究为I/R引起的神经损伤的治疗提供了新的见解和理论基础。提示靶向RPS27A和下游PSMD12/NF-κB信号轴进行药物开发可能代表I/R治疗的新方向。
方法：为了鉴定与脑I/R损伤相关的基因，采用高通量测序。使用基因本体论(GO)进一步分析了潜在的下游基因，京都基因和基因组百科全书（KEGG），和蛋白质-蛋白质相互作用(PPI)分析。对于实验模型，从小鼠大脑皮层组织中提取原代小胶质细胞和神经元。使用氧糖剥夺/复氧（OGD/R）技术在小胶质细胞中建立了体外脑I/R损伤模型。体内模型涉及通过大脑中动脉闭塞（MCAO）方法在小鼠中诱导脑I/R损伤。这些模型用于评估神经功能，免疫细胞浸润，和炎症因子释放。
结果：研究确定RPS27A是大脑I/R损伤的关键角色，PSMD12可能充当其下游监管机构。在OGD/R诱导的小胶质细胞中沉默RPS27A减少了炎症因子的释放并减少了神经元凋亡。此外,大脑皮层组织RPS27A沉默介导PSMD12/NF-κB轴,导致炎症因子释放减少，中性粒细胞浸润减少，并改善I/R损伤小鼠的脑损伤结果。
结论：RPS27A调节PSMD12/NF-κB信号轴的表达，导致小胶质细胞炎症因子的诱导，促进脑组织中的免疫细胞浸润，并加剧I/R小鼠的脑损伤。这项研究为I/R引起的神经损伤的治疗提供了新的见解和理论基础。提示靶向RPS27A和下游PSMD12/NF-κB信号轴进行药物开发可能代表I/R治疗的新方向。
