Endothelial YAP Signaling Promotes Blood-Spinal Cord Barrier Repair in Mice After Spinal Cord Injury

Area of Science:

• Neuroscience
• Cell Biology
• Regenerative Medicine

Background:

• Spinal cord injury (SCI) disrupts the blood-spinal cord barrier (BSCB).
• Molecular mechanisms of BSCB remodeling after SCI are not fully understood.
• Endothelial cells are crucial for BSCB integrity and repair.

Purpose of the Study:

• Investigate the role of Yes-associated protein (YAP) in endothelial cells during BSCB remodeling after SCI.
• Elucidate the molecular pathways involved in YAP-mediated BSCB repair.
• Assess the therapeutic potential of targeting YAP for SCI recovery.

Main Methods:

• Utilized YAP endothelial cell-specific knockout mice (YAP^TEK-cre/ERT2-CKO) in a mouse SCI model.
• Assessed BSCB integrity, endothelial cell proliferation, and tight junction status.
• Analyzed angiopoietin-1 (ANGPT1) expression and PI3K/AKT pathway activation.
• Investigated the effects of exogenous ANGPT1 treatment in vitro.

Main Results:

• YAP expression and activation were significantly upregulated in endothelial cells post-SCI.
• Endothelial YAP knockout exacerbated BSCB disruption and impaired motor function recovery.
• YAP-dependent BSCB repair involved ANGPT1 expression and PI3K/AKT pathway activation.
• Exogenous ANGPT1 partially rescued YAP deficiency effects on endothelial barrier function.

Conclusions:

• Endothelial YAP signaling is a critical regulator of BSCB remodeling and repair after SCI.
• The ANGPT1/PI3K/AKT pathway mediates YAP's effects on BSCB integrity.
• Targeting endothelial YAP represents a potential therapeutic strategy for improving outcomes after SCI.