Negative pressure induces p120-catenin-dependent adherens junction disassembly in keratinocytes during wound healing

Area of Science:

• Cell Biology
• Wound Healing
• Biomedical Engineering

Background:

• Negative-pressure (NP) therapy accelerates chronic wound healing by enhancing keratinocyte migration.
• NP treatment reduces E-cadherin expression, but the underlying molecular mechanisms require further elucidation.
• Understanding E-cadherin regulation under NP is crucial for optimizing wound healing therapies.

Purpose of the Study:

• To investigate the molecular mechanism of E-cadherin regulation in keratinocytes under NP treatment.
• To determine the role of p120-catenin in NP-induced E-cadherin modulation.
• To explore the signaling pathways involved in NP-mediated adherens junction dynamics.

Main Methods:

• HaCaT cells were subjected to ambient pressure (AP) and negative-pressure (NP) for 12 hours.
• Cell migration was assessed using traditional and electric wound healing assays.
• Western blotting, immunofluorescence, and overexpression/knockdown of p120-catenin were employed to analyze protein expression and localization.

Main Results:

• NP treatment increased Y228-phosphorylated p120-catenin, leading to its cytoplasmic translocation and decreased co-localization with E-cadherin at the plasma membrane.
• p120-catenin knockdown accelerated cell movement under AP, while Y228-phosphorylation-mimic mutants reduced E-cadherin membrane expression.
• Src inhibition blocked p120-catenin phosphorylation and impeded NP-induced cell migration.

Conclusions:

• Src-dependent phosphorylation of p120-catenin is a rapid response to NP, contributing to E-cadherin downregulation.
• NP-induced adherens junction disassembly, mediated by p120-catenin phosphorylation, accelerates wound healing.
• This study reveals a key molecular pathway regulating cell-cell adhesion dynamics during negative-pressure wound therapy.