Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function.

Area of Science:

• Biochemistry
• Dermatology
• Regenerative Medicine

Background:

• The CAR peptide (CARSKNKDC) is known to home to angiogenic neovessels.
• Wound healing is a complex process involving cell migration and tissue remodelling.
• Syndecan-4, a heparan sulfate proteoglycan, is critical for cell migration and wound repair.

Purpose of the Study:

• To investigate the therapeutic potential of systemically administered CAR peptide in promoting wound healing.
• To elucidate the molecular mechanisms underlying CAR peptide-mediated wound repair, focusing on syndecan-4.
• To determine the role of syndecan-4 in CAR peptide's efficacy in vivo.

Main Methods:

• Administration of CAR peptide to male mice with induced wounds.
• In vitro assessment of CAR peptide's effect on keratinocyte migration.
• Analysis of syndecan-4 expression in mouse skin wounds.
• Investigating the interaction between CAR peptide, syndecan-4, ARF6, and cytohesin-2.
• Evaluating wound re-epithelialization in syndecan-4-ablated mice treated with CAR peptide.

Main Results:

• Systemic administration of CAR peptide significantly accelerated wound closure and re-epithelialization in male mice.
• CAR peptide promoted keratinocyte migration in vitro.
• Syndecan-4 expression was localized to the epidermis and blood vessels in wounds and was essential for CAR peptide binding and internalization.
• CAR peptide induced syndecan-4-dependent activation of ARF6 via cytohesin-2, enhancing keratinocyte migration.
• Genetic ablation of syndecan-4 abolished CAR peptide-induced wound re-epithelialization.

Conclusions:

• CAR peptide enhances wound healing through a mechanism involving syndecan-4.
• CAR peptide activates syndecan-4-mediated signaling pathways, including ARF6 and cytohesin-2, to promote keratinocyte migration and re-epithelialization.
• CAR peptide represents a promising therapeutic agent for promoting wound healing with systemic administration but specific organ and cell targeting.