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  4. 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

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

Journal of Translational Medicine, 2025 · DOI: https://doi.org/10.1186/s12967-025-06095-0 · Published: January 8, 2025

Spinal Cord InjuryImmunologyGeneticsBioinformaticsBiomedical

Simple Explanation

This study investigates the roles of ferroptosis and immune responses in spinal cord injury (SCI) using bioinformatics analysis of multiple datasets. It identifies potential biomarkers, regulatory networks, and cell populations involved in these processes after SCI. The researchers explore the effects of nanolayered double hydroxide loaded with neurotrophic factor 3 (LDH-NT3) on microglial activation, immune responses, and ferroptosis in SCI both in vivo and in vitro. The study constructs TF-miRNA-mRNA networks, which may reveal the potential regulatory mechanisms underlying the inflammatory responses and ferroptosis post SCI.

Study Duration
Not specified
Participants
256 male and female C57BL/6 mice
Evidence Level
Not specified

Key Findings

  • 1
    A novel subcluster of microglia exhibiting M1 polarization and a ferroptosis phenotype is involved in SCI, potentially triggering neuroinflammation and neuronal degeneration.
  • 2
    NFKB1 may regulate the expression of CYBB and HMOX1 in a unique subcluster of M1 microglia within the middle SCI lesion, linking microglial ferroptosis and neuroinflammation.
  • 3
    NT3-chitosan or LDH-NT3 have potential effects on neuronal regeneration by reducing inflammatory responses and microglial ferroptosis.

Research Summary

The study identifies key biomarkers related to ferroptosis and the immune microenvironment after SCI, providing clues for subsequent studies at the transcriptional and single-cell levels. WGCNA identified hub gene module positively related to the time points after SCI. Also, DETIRGs and DEFIRGs were identified based on known FRGs and IRGs, respectively. The key mRNA-TF interaction pairs were all validated by ChIP-seq data. Based on the CMAP database, the study predicted the top 10 small-molecular drugs targeting the 2 DEFIRGs and 13 DETIRGs respectively.

Practical Implications

Therapeutic Targets

Identified hub genes and pathways offer potential targets for therapeutic interventions in SCI.

Diagnostic Markers

Specific genes identified in peripheral blood may serve as diagnostic markers for SCI.

Biomaterial Applications

LDH-NT3 can be utilized to construct a favorable microenvironment for functional recovery after SCI.

Study Limitations

  • 1
    Differences exist among mice, rats, and humans in immune system activation and response to SCI, limiting direct extrapolation of data to humans.
  • 2
    Drawing inference from disparate tissue types (e.g., brain and spinal cord) can introduce discrepancies into the results.
  • 3
    Data from post-mortem human SCI tissue samples may provide more reliable results than animal models for validation.

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