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Ferroptosis Transferrin Receptor Protein 1 (TFRC) Improves the Functional Prognosis After Ischemic Stroke by
Chunshu Rong1,2, Zhen Wei3,2, Xue Wang2,4
1Department of Encephalopathy, Hospital of Changchun University of Chinese Medicine, Changchun, Jilin, 130021, China.
Introduction:
Recent research indicates that ferroptosis plays a role in Ischemic Stroke (IS). This study aims to investigate the causal connections and underlying mechanisms involving Ferroptosis-related genes, Gut Microbiota (GM), and IS using the Mendelian Randomization (MR) approach.
Methods:
Both two-sample MR analysis and mediation analysis were employed in this study. Initially, the two-sample MR analysis assessed the causal relationship between Ferroptosis genes and IS. To examine the expression patterns of Ferroptosis genes, the GSE140275 dataset was utilized. The mediation analysis aimed to investigate the effect of Ferroptosis gene expression on GM and IS.
Results:
Results demonstrated that elevated expression of the TFRC gene was significantly and negatively associated with IS function. The TFRC gene influences the incidence of IS indirectly by modulating Megamonas GM. Our findings were further supported by sensitivity analyses, confirming their strong statistical validity. Additionally, six drugs for the prevention and treatment of IS were identified based on their binding to TFRC, and these molecules exhibited stable binding.
Discussion:
This study, by integrating multiple databases, employs two-sample Mendelian randomization and mediation analysis to reveal, for the first time, the causal association between the ferroptosis gene TFRC and IS. It was found that high expression of TFRC is a protective factor that improves IS function.
Conclusion:
This study reveals the role of TFRC in the progression of IS by regulating Megamonas GM. Regulating Megamonas may reduce the occurrence of IS.
