Bioinformatic analysis identifies GPR91 as a potential key gene in brain injury after deep hypothermic low flow
Song Puwei,
Xu Jiali,
Deqin Zhuoga,
Wu Kede,
Nishant Patel,
An Jia,
Qi Jirong,
Mo Xuming
Affiliations
Song Puwei
Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
Xu Jiali
Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
Deqin Zhuoga
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, 210093, China
Wu Kede
Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
Nishant Patel
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, 210093, China; Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China
An Jia
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, 210093, China
Qi Jirong
Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China; Corresponding author. Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Medical School of Nanjing Children University, Nanjing, 210093, China.
Mo Xuming
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, 210093, China; Department of Cardiothoracic Surgery, Children's Hospital of Nanjing Medical University, Nanjing, 210008, China; Corresponding author. Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Medical School of Nanjing University, Nanjing, 210093, China.
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.
