WW Domain-Binding Protein 2 Aggravates Neointimal Hyperplasia by Promoting Y-Box Binding Protein 1 Nuclear...

Area of Science:

• Vascular Biology
• Molecular Cardiology
• Oncogenic Signaling

Background:

• Restenosis after percutaneous coronary intervention (PCI) remains a clinical challenge.
• The molecular mechanisms underlying neointimal hyperplasia (NIH) are not fully understood.
• WW domain-binding protein 2 (WBP2) is an oncoprotein with an undefined role in vascular biology.

Purpose of the Study:

• To investigate the role of WBP2 in neointimal hyperplasia (NIH) and vascular smooth muscle cell (VSMC) proliferation.
• To elucidate the molecular mechanisms by which WBP2 influences vascular injury response.

Main Methods:

• Utilized a mouse carotid artery ligation (CAL) model to induce vascular injury.
• Assessed WBP2 expression, NIH extent (histopathology), and VSMC proliferation/migration (FUCCI, Transwell assays).
• Investigated WBP2's interaction with Y-box binding protein 1 (YBX1) and its effect on YBX1 phosphorylation and nuclear translocation.

Main Results:

• WBP2 expression increased post-vascular injury and with PDGF-BB stimulation.
• WBP2 knockdown reduced NIH and VSMC proliferation, while overexpression exacerbated these effects.
• WBP2 facilitates YBX1 nuclear translocation via RSK-mediated phosphorylation, activating proliferative genes.

Conclusions:

• WBP2 promotes NIH and VSMC proliferation by enhancing YBX1 nuclear translocation.
• WBP2 is a key mediator in the vascular injury response.
• WBP2 represents a potential therapeutic target for managing restenosis.