DAPK1 Ablation Promotes Wound Healing by Keratinocyte Modulation

Area of Science:

• Biochemistry
• Cell Biology
• Regenerative Medicine

Background:

• Death-associated protein kinase 1 (DAPK1) is crucial for skin repair but its role in oral mucosa healing is unknown.
• Understanding DAPK1's function in oral mucosal repair is vital for developing new therapeutic strategies.

Purpose of the Study:

• To investigate the role of DAPK1 in oral mucosal wound healing.
• To explore the therapeutic potential of targeting DAPK1 for accelerated oral wound repair.

Main Methods:

• Generated global Dapk1 knockout mice to create palatal wounds.
• Performed in vitro studies on human oral keratinocytes.
• Utilized transcriptome sequencing to analyze signaling pathways.
• Developed and tested a DAPK1 inhibitor (HS-38) microneedle patch for drug delivery.

Main Results:

• DAPK1 deficiency significantly accelerated oral wound closure in mice.
• DAPK1 modulates oral keratinocyte proliferation and migration.
• Loss of DAPK1 activates Wnt signaling and suppresses innate immunity mediators.
• The HS-38 microneedle patch enhanced wound healing in normal and diabetic mice.

Conclusions:

• DAPK1 plays an inhibitory role in oral mucosal repair.
• Targeting DAPK1 enhances epithelial regeneration and reduces inflammation.
• A DAPK1 inhibitor microneedle patch is a promising approach for accelerating oral wound healing.