Deubiquitinase UCHL1 promotes angiogenesis and blood–spinal cord barrier function recovery after spinal cord injury by stabilizing Sox17

Cellular and Molecular Life Sciences, 2024 · DOI: https://doi.org/10.1007/s00018-024-05186-3 · Published: February 18, 2024

Spinal Cord Injury Cardiovascular Science Neurology

Simple Explanation

This study investigates how a protein called UCHL1 affects recovery after spinal cord injury (SCI). It focuses on the blood-spinal cord barrier (BSCB), which protects the spinal cord. The researchers found that UCHL1 helps to stabilize another protein, Sox17, which is important for the growth of new blood vessels (angiogenesis) and the repair of the BSCB after SCI. By studying mice with and without UCHL1, the study showed that UCHL1 promotes angiogenesis and BSCB function recovery after SCI by stabilizing Sox17, suggesting a potential new target for SCI treatment.

Study Duration

Not specified

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Sox17 is predominantly localized in endothelial cells and is significantly upregulated after SCI and in LPS-treated brain microvascular endothelial cells.
2
In vivo overexpression of Sox17 promoted angiogenesis and functional recovery after injury.
3
The deubiquitinase UCHL1 promotes angiogenesis and restoration of BSCB function after injury by stabilizing Sox17.

Research Summary

This study investigates the role of the deubiquitinase UCHL1 in promoting angiogenesis and blood-spinal cord barrier (BSCB) function recovery after spinal cord injury (SCI) by stabilizing Sox17. The findings demonstrate that UCHL1 interacts with Sox17, a transcription factor predominantly localized in endothelial cells, and stabilizes it, influencing angiogenesis and BSCB repair following injury. Conditional knockout experiments further validated that UCHL1 promotes angiogenesis and restoration of BSCB function after injury by stabilizing Sox17, presenting a novel therapeutic target for treating SCI.

Practical Implications

Therapeutic Target

Sox17 may serve as a potential target for the treatment of SCI.

Endothelial Cell Regeneration

UCHL1-mediated post-translational modifications of Sox17 in endothelial cells are important.

Novel Mechanism

This study reveals a novel mechanism of endothelial cell regeneration and BSCB repair following SCI, potentially opening avenues for new therapeutic targets for SCI.

Study Limitations

1
The exact mechanism of Sox17 downregulation in the early phase of SCI is unclear.
2
The study primarily considers UCHL1 as a deubiquitinase acting on Sox17, acknowledging that UCHL1 may have direct effects on endothelial cells after injury.
3
The regeneration of vascular endothelium and restoration of barrier function after injury involve complex cascades of reactions, and a single isolated mechanism is insufficient to explain this intricate process.

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