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CASP8 Is a Potential Therapeutic Target and Is Correlated with Pyroptosis in Traumatic Brain Injury
Gengshui Zhao1, Yongqi Fu2, Chao Yang3
1Department of Neurosurgery, The People's Hospital of Hengshui City, Hengshui, China.
Background:
Traumatic brain injury (TBI) is a major cause of neurological and psychological problems, especially long-term disability. The purpose of this article is to explore molecular mechanisms linking TBI and pyroptosis with the aim of providing a promising target for future therapeutic interventions.
Methods:
GSE104687 microarray dataset was downloaded from the Gene Expression Omnibus database to obtain differential expressed genes. Meanwhile, pyroptosis-related genes were screened from GeneCards database, and the overlapped genes were considered as the pyroptosis-related genes in TBI. The immune infiltration analysis was conducted to quantify lymphocyte infiltration levels. Moreover, we researched the relevant microRNAs (miRNAs) and transcription factors and investigated the interactions and functions of miRNAs. In addition, the validation set and in vivo experiment further verified the expression of hub gene.
Results:
Altogether, we found 240 differential expressed genes in GSE104687 and 254 pyroptosis-related genes in the GeneCards database, and the overlapped gene was caspase 8 (CASP8). Immune Infiltration Analysis suggested the abundance of Tregs cells was significantly higher in TBI group. The NKT and CD8+ Tem were positively correlated with the expression levels of CASP8. The most significant term regarding CASP8 in Reactome pathways analysis was related to NF-kappaB. A total of 20 miRNAs and 25 transcription factors associated with CASP8 were obtained. After investigating the interactions and functions of miRNAs, the NF-kappaB-related signaling pathway was still enriched with a relatively low P-value. The validation set and in vivo experiment further verified the expression of CASP8.
Conclusions:
Our study showed the potential role of CASP8 in pathogenesis of TBI, which may provide a new target for individualized therapy and drug development.
Insights
This study identifies Caspase 8 (CASP8) as a key molecular link between traumatic brain injury (TBI) and pyroptosis. Targeting CASP8 may offer new therapeutic strategies for TBI patients.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Traumatic brain injury (TBI) is a significant cause of long-term neurological and psychological disability.
- Understanding the molecular mechanisms underlying TBI is crucial for developing effective treatments.
- Pyroptosis, a programmed cell death pathway, is implicated in various inflammatory conditions.
Purpose of the Study:
- To explore the molecular mechanisms linking TBI and pyroptosis.
- To identify potential therapeutic targets for TBI.
- To investigate the role of Caspase 8 (CASP8) in TBI pathogenesis.
Main Methods:
- Utilized the GSE104687 microarray dataset to identify differentially expressed genes in TBI.
- Screened pyroptosis-related genes from the GeneCards database.
- Performed immune infiltration analysis, miRNA, and transcription factor analysis.
- Validated findings using a validation set and in vivo experiments.
Main Results:
- Identified Caspase 8 (CASP8) as the overlapping gene between TBI and pyroptosis.
- Observed significantly higher Treg cell abundance in the TBI group.
- Found positive correlations between CASP8 expression and NKT and CD8+ Tem cells.
- Linked CASP8 to the NF-kappaB signaling pathway, further supported by miRNA analysis.
Conclusions:
- Caspase 8 (CASP8) plays a potential role in the pathogenesis of TBI.
- CASP8 may serve as a novel therapeutic target for TBI.
- Findings could inform individualized therapy and drug development for TBI.
