Poly(ADP-ribose) polymerase family member 14 promotes functional recovery after spinal cord injury through regulating microglia M1/M2 polarization via STAT1/6 pathway

Neural Regeneration Research, 2023 · DOI: https://doi.org/10.4103/1673-5374.357909 · Published: October 11, 2022

Simple Explanation

This research investigates the role of Poly(ADP-ribose) polymerase family member 14 (PARP14) in spinal cord injury (SCI) recovery. It was found that PARP14 is upregulated in the injured spinal cord. Silencing PARP14 expression aggravated functional impairment after SCI, accompanied by neuronal apoptosis and neuroinflammation. PARP14 knockdown promoted a shift from M2-polarized microglia (anti-inflammatory) to M1-polarized microglia (pro-inflammatory). PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.

Study Duration

28 days

Participants

176 female C57BL/6J mice

Evidence Level

Not specified

Key Findings

1
PARP14 expression is upregulated in spinal cord tissues after SCI, suggesting a compensatory mechanism.
2
PARP14 deficiency exacerbates SCI-induced neuronal apoptosis, as evidenced by increased levels of pro-apoptotic factors and decreased levels of anti-apoptotic factors.
3
PARP14 deficiency exacerbates the shift of M2-polarized microglia to M1-polarized microglia in mice with SCI, promoting neuroinflammation.

Research Summary

This study explored the protective role of PARP14 in SCI, finding that PARP14 expression increases at the injury site in a mouse model of SCI, and its knockdown worsens SCI. Both in vivo and in vitro experiments revealed that PARP14 inhibits microglia M1 polarization, likely by blocking the STAT1 pathway, and promotes microglia M2 polarization by activating the STAT6 pathway. The study also demonstrated that PARP14 silencing promoted SCI-induced bone loss, suggesting PARP14 as a potential therapeutic target for SCI.

Practical Implications

Therapeutic Target

PARP14 may serve as a promising therapeutic target for SCI treatment.

Microglia Polarization

Modulating microglia polarization via PARP14 could alleviate neuroinflammation and promote functional recovery.

Bone Loss Prevention

Targeting PARP14 may help prevent or reduce SCI-induced bone loss.

Study Limitations

1
The study acknowledges that the PARP14-mediated microglial phenotype switch may promote SCI progression, but whether PARP14 is involved through other pathways requires further study.
2
The study acknowledges that the absence of significant bone loss observed in SCI mice compared to sham-operated mice was most likely because of the moderate injury induced.
3
The results should be confirmed with a larger sample size.

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