PGK1 Is Involved in the HIF-1 Signaling Pathway as a Hub Gene for Ferroptosis After Traumatic Brain Injury

Area of Science:

• Neuroscience
• Biochemistry
• Bioinformatics

Background:

• The mechanisms of ferroptosis in traumatic brain injury (TBI) remain largely unknown.
• Identifying key molecular players is crucial for understanding TBI pathogenesis and developing therapeutic strategies.

Purpose of the Study:

• To identify key molecules and pathways involved in ferroptosis following TBI using bioinformatics analysis.
• To investigate the role of phosphoglycerate kinase 1 (PGK1) in TBI-associated ferroptosis.

Main Methods:

• Downloaded and analyzed the GSE128543 dataset from the Gene Expression Omnibus (GEO) database.
• Utilized weighted gene co-expression network analysis (WGCNA) to identify TBI-associated gene modules.
• Performed differential gene expression analysis and protein-protein interaction network analysis.
• Constructed a TBI mouse model and analyzed PGK1 and HIF-1α expression in cerebrospinal fluid (CSF) of clinical patients.

Main Results:

• Identified 60 differentially expressed genes (DEGs) related to ferroptosis and glycolysis/gluconeogenesis.
• The hypoxia-inducible factor-1 (HIF-1) signaling pathway was found to be critical.
• Discovered 20 hub genes, including PGK1, with PGK1 and HIF-1α expression increasing post-TBI in mice.
• PGK1 expression in CSF negatively correlated with brain injury severity and cognitive function (Glasgow Coma Scale).

Conclusions:

• PGK1 is a potential hub gene in TBI-associated ferroptosis, mediated by the HIF-1 signaling pathway.
• PGK1 expression levels may serve as a prognostic biomarker for neurological injury severity after TBI.
• Further research into PGK1's mechanism could lead to novel therapeutic targets for TBI.