UTX/KDM6A Deletion Promotes Recovery of Spinal Cord Injury by Epigenetically Regulating Vascular Regeneration

Molecular Therapy, 2019 · DOI: https://doi.org/10.1016/j.ymthe.2019.08.009 · Published: December 1, 2019

Spinal Cord Injury Regenerative Medicine Genetics

Simple Explanation

Spinal cord injuries can cause damage to blood vessels, which hinders recovery. This study explores how a protein called UTX affects blood vessel regeneration after a spinal cord injury. The researchers found that UTX levels increase after injury. Reducing UTX in endothelial cells (cells lining blood vessels) promoted blood vessel growth and improved recovery in mice. UTX affects the expression of a microRNA called miR-24, which in turn regulates blood vessel growth. By manipulating UTX and miR-24, the researchers were able to influence blood vessel regeneration and functional recovery after spinal cord injury.

Study Duration

Not specified

Participants

Mice (C57BL/6J male mice, UTXflox/flox mouse strain, Tek-Cre mouse strain), Human umbilical vein endothelial cells (HUVECs)

Evidence Level

Not specified

Key Findings

1
UTX expression increases in endothelial cells following spinal cord injury in mice.
2
Knockout of UTX in endothelial cells promotes vascular regeneration and functional recovery after spinal cord injury.
3
UTX directly binds to and demethylates the promoter of miR-24 in endothelial cells, influencing its expression.

Research Summary

This study investigates the role of UTX, a histone demethylase, in vascular regeneration following spinal cord injury (SCI). The researchers found that UTX expression increases in endothelial cells post-SCI. Knocking out UTX in endothelial cells promoted angiogenesis and improved neurological function in a mouse model of SCI. This effect was mediated by UTX's regulation of miR-24, a microRNA involved in endothelial cell function. The study suggests that UTX deletion can epigenetically promote vascular regeneration and functional recovery post-SCI by forming a regulatory network with miR-24, offering potential therapeutic targets for SCI treatment.

Practical Implications

Therapeutic Target Identification

Targeting UTX and miR-24 could be a potential therapeutic strategy for promoting vascular regeneration and functional recovery after spinal cord injury.

Epigenetic Intervention

The study highlights the importance of epigenetic regulation in SCI and suggests that epigenetic interventions could be used to promote recovery.

Neurovascular Unit Focus

The research reinforces the importance of considering the neurovascular unit in SCI treatment and highlights the role of vascular regeneration in neurological recovery.

Study Limitations

1
The study was conducted primarily in mice, and further research is needed to determine if the findings translate to humans.
2
The precise mechanisms by which miR-24 regulates vascular regeneration require further investigation.
3
The long-term effects of UTX knockout on spinal cord function were not fully explored.

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