Upregulation of circ0000381 attenuates microglial/ macrophage pyroptosis after spinal cord injury

Neural Regeneration Research, 2024 · DOI: https://doi.org/10.4103/1673-5374.386399 · Published: June 1, 2024

Simple Explanation

Spinal cord injury (SCI) often leads to inflammation, which worsens the damage. Pyroptosis, a form of inflammatory cell death in microglia/macrophages, contributes to this inflammation. This study explores how circRNAs, specifically circ0000381, affect pyroptosis after SCI. The researchers found that circ0000381 levels increase in a rat model of SCI. They suggest circ0000381 may act like a sponge, soaking up a molecule called miR-423-3p. By doing so, it reduces the production of NLRP3, a key protein involved in pyroptosis. In essence, the upregulation of circ0000381 might be a protective response to lessen the severity of inflammation-driven cell death following spinal cord injury. This finding suggests circ0000381 could be a potential target for new SCI treatments.

Study Duration

42 days

Participants

65 adult female Wistar rats

Evidence Level

Not specified

Key Findings

1
Circ0000381 expression is upregulated in the spinal cord of rats after SCI and in LPS-treated microglia/macrophages in vitro.
2
Knockdown of circ0000381 enhances microglial/macrophage pyroptosis, increasing NLRP3 expression.
3
Circ0000381 acts as an endogenous sponge for miR-423-3p, inhibiting its activity and limiting microglial/macrophage pyroptosis.

Research Summary

This study investigates the role of circ0000381 in regulating microglia/macrophage pyroptosis following spinal cord injury (SCI). The findings suggest that circ0000381 upregulation after SCI may be a compensatory mechanism to attenuate pyroptosis by acting as a sponge for miR-423-3p, thus reducing NLRP3 expression. The study identifies circ0000381 as a potential therapeutic target for SCI treatment, warranting further investigation into its effectiveness in vivo and underlying mechanisms.

Practical Implications

Therapeutic Target

Circ0000381 may serve as a novel therapeutic target for the treatment of spinal cord injury by attenuating microglial/macrophage pyroptosis.

Neuroprotective Mechanism

Upregulation of circ0000381 may represent a neuroprotective mechanism to limit inflammation-driven cell death following SCI.

MiRNA Sponge

Circ0000381 can bind to miR-423-3p and act as an endogenous sponge to inhibit miR-423-3p activity, thus attenuating spinal microglial/macrophage pyroptosis.

Study Limitations

1
Experiments exploring the regulatory role of circ0000381 in microglial/macrophage pyroptosis after SCI were primarily conducted in cell lines.
2
The study was conducted in female rats only, which may limit the generalizability of the findings.
3
It remains to be determined whether other differentially expressed circRNAs also play a role in regulating microglial/macrophage pyroptosis after SCI.

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