生物信息学分析确定GPR91是深低温低流量脑损伤中的一个潜在关键基因。
Bioinformatic analysis identifies GPR91 as a potential key gene in brain injury after deep hypothermic low flow.
作者信息
Puwei Song, Jiali Xu, Zhuoga Deqin, Kede Wu, Patel Nishant, Jia An, Jirong Qi, Xuming Mo
机构信息
Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China.
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, 210093, China.
出版信息
Heliyon. 2023 Apr 15;9(5):e15286. doi: 10.1016/j.heliyon.2023.e15286. eCollection 2023 May.
PURPOSE
Explore the transcription change of brain ischemia and reperfusion injury after deep hypothermic low flow.
METHOD
The data from PRJNA739516 and GSE104036 were obtained for the differentially expressed genes identification, functional enrichment analysis, gene set enrichment analysis, protein-protein interaction construction and hub gene identification. Oxygen and glucose deprivation model was set to validate the hub gene and explore the detailed brain injury mechanism.
RESULT
Interleukin, immunological response, NF-κB signaling pathway, G protein-coupled receptor signaling pathway and NLRP inflammatory are functional pathway were enriched in differentially expressed genes analysis. Sucnr1, Casr, Cxcr4, C5ar1, Tas2r41, Tas2r60 and Hcar2 were identified and verified in the OGD model. Knocking down GPR91 reduces the inflammatory response after OGD and GPR91 may be involved in the inflammatory pre-reaction through the synergistic activation of NF-κB, NLRP3, and IL-1β respectively.
CONCLUSION
Our study found that Interleukin, immunological response, NF-κB signaling pathway, G protein-coupled receptor signaling pathway and NLRP inflammatory are all associated with brain ischemia and reperfusion injury after deep hypothermic low flow and GPR91 can activate NF-κB/NLRP3 pathway and trigger the release of IL-1β in this progress.
目的
探讨深低温低流量后脑缺血再灌注损伤的转录变化。
方法
获取来自PRJNA739516和GSE104036的数据，用于差异表达基因鉴定、功能富集分析、基因集富集分析、蛋白质-蛋白质相互作用构建和枢纽基因鉴定。设置氧糖剥夺模型以验证枢纽基因并探索详细的脑损伤机制。
结果
在差异表达基因分析中，白细胞介素、免疫反应、NF-κB信号通路、G蛋白偶联受体信号通路和NLRP炎症相关功能通路得到富集。在氧糖剥夺模型中鉴定并验证了Sucnr1、Casr、Cxcr4、C5ar1、Tas2r41、Tas2r60和Hcar2。敲低GPR91可减轻氧糖剥夺后的炎症反应，并且GPR91可能分别通过NF-κB、NLRP3和IL-1β的协同激活参与炎症预反应。
结论
我们的研究发现，白细胞介素、免疫反应、NF-κB信号通路、G蛋白偶联受体信号通路和NLRP炎症均与深低温低流量后的脑缺血再灌注损伤相关，并且GPR91在这一过程中可激活NF-κB/NLRP3通路并触发IL-1β的释放。
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