ArticleJournal of translational medicine2025
Ferroptosis-related genes participate in the microglia-induced neuroinflammation of spinal cord injury via NF-κB signaling: evidence from integrated single-cell and spatial transcriptomic analysis.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- MicroRNA-Ferroptosis-Spinal Cord Injury: A Complex Interplay in Neurodegeneration and Repair.International journal of molecular sciences · 2026Review
- M2 macrophage-derived exosomes delivering haptoglobin and interleukin-10 plasmids for synergistic therapy of intracerebral hemorrhage.Bioactive materials · 2026Article
- Dysosma versipellis is associated with cholestatic hepatotoxicity potentially involving FXR-SHP-CYP7A1/BSEP-MRP2 axis disruption: A multi-omics-driven mechanistic investigation based on the toxicological evidence chain (TEC) concept.Journal of molecular histology · 2026Article
- Time‑resolved multi-omic analysis of paclitaxel exposure in human iPSC‑derived sensory neurons unveils mechanisms of chemotherapy‑induced peripheral neuropathy.Cell death & disease · 2026Article
- Ferroptosis-associated myeloid cell heterogeneity and inflammatory amplification following spinal cord injury.Frontiers in immunology · 2026Article
- A four-dimensional spatial atlas of spinal cord injury reveals predominant Spp1-integrin signaling driving microglia-fibroblast crosstalk in fibrotic niches.Frontiers in immunology · 2026Article
- Iron-driven secondary injury after intracranial hemorrhage: mitochondrial dysfunction and ferroptosis.Frontiers in neuroscience · 2026Review
- Lysosomes as chemical and metabolic organizers of central nervous system injury and repair.Frontiers in chemistry · 2026Review
- BRD-K20733377 inhibits ferroptosis and alleviates intervertebral disc degeneration via the STAT3/NFKB1 axis: a multiapproach study.Stem cell research & therapy · 2025Article
- Precision Recovery After Spinal Cord Injury: Integrating CRISPR Technologies, AI-Driven Therapeutics, Single-Cell Omics, and System Neuroregeneration.International journal of molecular sciences · 2025Review
- Microglial pyroptosis as a therapeutic target after traumatic spinal cord injury: current progress and future directions.Frontiers in immunology · 2025Review
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Authors and funding
9 authors.
Funding
Abstract
backgroundFerroptosis and immune responses are critical pathological events in spinal cord injury (SCI), whereas relative molecular and cellular mechanisms remain unclear.
methodsMicro-array datasets (GSE45006, GSE69334), RNA sequencing (RNA-seq) dataset (GSE151371), spatial transcriptome datasets (GSE214349, GSE184369), and single cell RNA sequencing (scRNA-seq) datasets (GSE162610, GSE226286) were available from the Gene Expression Omnibus (GEO) database. Through weighted gene co-expression network analysis and differential expression analysis in GSE45006, we identified differentially expressed time- and immune-related genes (DETIRGs) associated with chronic SCI and differentially expressed ferroptosis- and immune-related genes (DEFIRGs), which were validated in GSE151371. Protein-protein interaction and microRNA-mRNA-transcription factor regulatory networks were constructed based on Search Tool for the Retrieval of Interacting Genes (STRING) and NetworkAnalyst, respectively, which were validated by chromatin immunoprecipitation followed by sequencing (ChIP-seq). Cell subclusters and unique features of microglia in SCI were identified by single-cell transcriptomic analysis, which were validated in GSE226286. Spatial expression patterns of DETIRGs and DEFIRGs were validated in brain injury (GSE214349) and SCI (GSE184369). Potential mechanisms underlying neuronal regeneration by neurotrophin-3 (NT3)-chitosan were revealed by transcriptomic analyses in GSE69334. Immune- and ferroptosis-related mechanisms of nanolayered double hydroxide loaded with NT3 (LDH-NT3) were investigated in vivo and in vitro.
resultsGBP2, TEC, UNC93B1, PLXNC1, NFATC1, IL10RB, and TLR8 were DETIRGs represented chronic SCI-specific genes and peripheral blood biomarkers. NFKB1 may regulate expression of CYBB and HMOX1 in a unique subcluster of M1 microglia within the middle SCI lesion, establishing links between microglial ferroptosis and neuroinflammation. Reduced inflammatory responses and microglial ferroptosis were potential effects of NT3-chitosan or LDH-NT3 on neuronal regeneration.
conclusionsA novel subcluster of microglia exhibiting M1 polarization and ferroptosis phenotype was involved in SCI. These microglia may trigger neuroinflammation and induce neuronal degeneration within the middle site of SCI, which might be inhibited by NT3-chitosan or LDH-NT3.
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