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  4. Comparative Transcriptomics of Rat and Axolotl After Spinal Cord Injury Dissects Differences and Similarities in Inflammatory and Matrix Remodeling Gene Expression Patterns

Comparative Transcriptomics of Rat and Axolotl After Spinal Cord Injury Dissects Differences and Similarities in Inflammatory and Matrix Remodeling Gene Expression Patterns

Frontiers in Neuroscience, 2018 · DOI: 10.3389/fnins.2018.00808 · Published: November 13, 2018

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

Following spinal cord injury, mammals experience inflammation and tissue scarring, leading to permanent loss of function. Axolotls, however, can fully regenerate their spinal cord without scarring after injury. This study compares gene expression patterns in rats and axolotls after spinal cord injury to identify molecules and pathways involved in tissue responses. The researchers analyzed transcriptomic datasets from rats and axolotls, focusing on shared genes with similar or differential expression patterns at days 1, 3, and 7 after spinal cord injury. They used computational tools to describe system-wide differences and similarities between the two species, highlighting key differentially regulated genes. The study found that extracellular matrix genes were upregulated in both species after spinal cord injury, suggesting the importance of matrix remodeling in wound healing. Additionally, the transcription factor SP1 was consistently upregulated in rats but unchanged in axolotls, indicating its potential role in regulating inflammatory response genes in rats.

Study Duration
7 Days
Participants
Rats: 4 sham vs. 4 injured spinal cord samples. Axolotls: 3 uninjured vs. 3 injured spinal cord replicates; each replicate is a pool of 10 axolotl spinal cords
Evidence Level
Transcriptomics analysis

Key Findings

  • 1
    Extracellular matrix genes were upregulated in both rats and axolotls after spinal cord injury at all time points (days 1, 3, and 7), indicating the importance of extracellular matrix remodeling in wound healing.
  • 2
    The transcription factor SP1 was consistently upregulated in rats but remained unchanged in axolotls after spinal cord injury. SP1 was predicted as a potential transcriptional regulator of classic inflammatory response genes in rats.
  • 3
    Genes associated with neuron projection were upregulated in axolotls but downregulated in rats, suggesting differences in spinal cord regeneration capabilities between the two species.

Research Summary

This study compares gene expression patterns in rats and axolotls after spinal cord injury to understand the differences between regeneration and scarring mechanisms. The researchers performed a four-way intersection of rat and axolotl transcriptomic datasets to identify shared genes with similar or differential expression. The analysis revealed that extracellular matrix genes were upregulated in both species, while the transcription factor SP1 was upregulated only in rats. Further analysis showed that SP1 might control classic inflammatory signaling genes in rats after spinal cord injury. The study provides an extensive comparative platform between a non-regenerating mammal and a regenerating urodele after spinal cord injury. It highlights the importance of understanding consistent molecular differences and similarities for improving regeneration strategies.

Practical Implications

Targeting Extracellular Matrix Remodeling

The consistent upregulation of extracellular matrix genes in both rats and axolotls suggests that modulating matrix remodeling could be a potential therapeutic target for improving spinal cord injury outcomes.

Inhibiting SP1 Activity

The upregulation of SP1 in rats and its association with inflammatory genes suggests that inhibiting SP1 activity could reduce the maladaptive inflammatory response after spinal cord injury in mammals.

Comparative Studies for Regeneration Strategies

Further comparative studies between regenerating and non-regenerating species are needed to identify molecular mechanisms that control scarless repair and regeneration, potentially leading to new strategies for enhancing functional repair in mammals.

Study Limitations

  • 1
    The study involves analysis of datasets derived from two highly different species and different labs, which could introduce variability.
  • 2
    The axolotl microarray IDs were matched to human orthologous genes, which might not perfectly represent the axolotl genome.
  • 3
    Injury models could drastically affect gene expression, and future studies need to be carefully designed in terms of injury models.

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