Astrocytic YAP Promotes the Formation of Glia Scars and Neural Regeneration after Spinal Cord Injury

The Journal of Neuroscience, 2020 · DOI: https://doi.org/10.1523/JNEUROSCI.2229-19.2020 · Published: March 25, 2020

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates the role of Yes-associated protein (YAP) in the formation of glial scars after spinal cord injury (SCI). It was found that YAP is upregulated and activated in astrocytes after SCI. The research demonstrates that conditional knockout of YAP in astrocytes inhibits astrocytic proliferation, impairs glial scar formation, and inhibits axonal regeneration, leading to impaired behavioral recovery after SCI in mice. The study also uncovers a bFGF-RhoA-YAP-p27Kip1 pathway that positively regulates astrocytic proliferation after SCI, suggesting this pathway may be a potential therapeutic strategy for SCI patients.

Study Duration

28 days

Participants

C57BL/6 WT male mice, yapf/f, and yapGFAP-CKO male mice

Evidence Level

Not specified

Key Findings

1
YAP was upregulated and activated in astrocytes of C57BL/6 male mice after SCI in a Hippo pathway-dependent manner.
2
Conditional knockout of yap in astrocytes significantly inhibited astrocytic proliferation, impaired the formation of glial scars, inhibited the axonal regeneration, and impaired the behavioral recovery of C57BL/6 male mice after SCI.
3
bFGF or XMU-MP-1 injection activated YAP signaling and promoted the formation of glial scars and the functional recovery of mice after SCI.

Research Summary

This study investigates the function of Yes-associated protein (YAP) in the formation of glial scars after spinal cord injury (SCI) through regulation of astrocyte proliferation. YAP promotes the proliferation of astrocytes through negatively controlling nuclear distribution of p27Kip1 mediated by CRM1. Activation of YAP by bFGF or XMU-MP-1 injection promotes the formation of glial scar and the functional recovery of mice after SCI.

Practical Implications

Therapeutic Target Identification

The bFGF-RhoA-YAP-p27Kip1 axis may be a potential therapeutic target for SCI patients.

Drug Development

Development of drugs targeting the YAP signaling pathway could promote glial scar formation and functional recovery after SCI.

Regenerative Medicine

Understanding YAP's role in neural regeneration may lead to new strategies for promoting axon regeneration and functional recovery after SCI.

Study Limitations

1
The study is limited to male mice, and the results may not be generalizable to females.
2
The study focuses on a clip-compressive SCI model, and the findings may not be applicable to other types of SCI.
3
The precise mechanisms by which YAP regulates CRM1 expression require further investigation.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury