The potential mechanisms of skin wound healing mediated by tetrapeptides from sea cucumber

Numerous food-derived natural bioactive peptides have excellent skin wound healing potential. Herein, we reported the capacity of sea cucumber derived tetrapeptides VTPY and VLLY to promote wound healing. Our study revealed that the two peptides significantly contribute to the healing of skin wounds by promoting re-epithelialization, collagen and lipid regeneration for skin appendage remodeling, and enhancing angiogenesis both in vitro and in vivo. VTPY and VLLY significantly accelerate the migration of keratinocytes to seal the wound surface, as well as facilitate collagen regeneration by promoting the phosphorylation of EKR and P-38. Meanwhile, VTPY and VLLY further enhance angiogenesis and lipid regeneration via upregulating expression of VEGF and eNOS, and triggering ERK/AKT signaling. VTPY works better than VLLY. These findings indicate that sea cucumber derived tetrapeptide VTPY and VLLY can serve as natural food source-derived candidate for promoting skin wound healing.