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Bioinformatics Analysis Identifies Potential Ferroptosis Key Genes in the Pathogenesis of Intracerebral Hemorrhage
Tongye Liu1, Xinhe Li1, Yiteng Cui1
1Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Insights
This study identifies key molecules like MAPK1 involved in ferroptosis after intracerebral hemorrhage (ICH). Exercise intervention, specifically treadmill training, shows potential as an antioxidant therapy to reduce neuronal ferroptosis in ICH.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Intracerebral hemorrhage (ICH) is a severe neurological condition with unclear ferroptosis mechanisms.
- Identifying key molecular players in ferroptosis is crucial for developing effective therapeutic strategies for ICH.
Purpose of the Study:
- To identify key molecules and pathways involved in ferroptosis following intracerebral hemorrhage using bioinformatics.
- To explore the potential of exercise intervention as a therapeutic approach for mitigating ferroptosis in ICH.
Main Methods:
- Downloaded and analyzed the GSE24265 dataset from the Gene Expression Omnibus (GEO).
- Performed bioinformatics analysis, including protein-protein interaction (PPI) network construction, to identify differentially expressed genes (DEGs).
- Generated an ICH rat model for exercise intervention (treadmill training) and assessed gene expression via qRT-PCR.
Main Results:
- Identified 45 DEGs, predominantly associated with TNF signaling and oxidative stress, with MAPK1 highlighted as a key gene.
- In ICH rats, MAPK1, ATF4, SLC2A1, and TNFAIP3 were upregulated, while MAPK8 was downregulated.
- Treadmill training modulated gene expression, increasing anti-inflammatory molecules (TNFAIP3, SLC2A1) and decreasing pro-ferroptotic genes (MAPK1, ATF4, MAPK8).
Conclusions:
- The MAPK1-related mRNA-miRNA-lncRNA interaction chain may serve as a biomarker for ferroptosis in ICH.
- Treadmill training demonstrates potential as an antioxidant therapy to reduce neuronal ferroptosis in intracerebral hemorrhage.
Abstract:
Intracerebral hemorrhage (ICH) is a dangerous neurological disease. The mechanism of ferroptosis in ICH remains unclear. Using bioinformatics analysis, we aimed to identify the key molecules involved in ferroptosis and provide treatment targets for ICH to further explore the mechanism of ferroptosis in ICH. GSE24265 was downloaded from the Gene Expression Omnibus (GEO) dataset and intersected with ferroptosis genes. A total of 45 differentially expressed genes (DEGs) were selected, most of which were involved in the TNF signaling pathway and oxidative stress response. Key modules constructed by the protein-protein interaction (PPI) network analysis and screening of genes related to the TNF signaling pathway led to the confirmation of the following genes of interest: MAPK1, MAPK8, TNFAIP3, ATF4, and SLC2A1. Moreover, MAPK1 was one of the key genes related to TNF signaling and oxidative stress, and it may play an important role in ferroptosis after cerebral hemorrhage. The MAPK1-related molecules included hsa-miR-15b-5P, hsa-miR-93-5P, miR-20b-5p, SNHG16, XIST, AC084219.4, RP11-379K17.11, CTC-444N24.11, GS1-358P8.4, CTB-89H12.4, RP4-773N10.5, and FGD5-AS1. We also generated a hemorrhage rat model, which was used to conduct exercise intervention in ICH rats, and qRT-PCR was used to assess the expression levels of our genes of interest. The mRNA levels after cerebral hemorrhage showed that MAPK1, ATF4, SLC2A1, and TNFAIP3 were upregulated, whereas MAPK8 was downregulated. Treadmill training increased the expression of anti-inflammatory molecules TNFAIP3 and SLC2A1 and reduced the expression of MAPK1, ATF4, and MAPK8, indicating that treadmill training may be utilized as antioxidant therapy to decrease neuronal ferroptosis. The results of this study indicated that the MAPK1-related mRNA-miRNA-lncRNA interaction chain could be potentially employed as a biomarker of the inception and progression of ferroptosis after cerebral hemorrhage.
