Characterization and mechanism of action of amphibian-derived wound-healing-promoting peptides

Wound-healing-promoting peptides are excellent candidates for developing wound-healing agents due to their small size and low production cost. Amphibians are one of the major sources of bioactive peptides, including wound-healing-promoting peptides. So far, a series of wound-healing-promoting peptides have been characterized from amphibians. We hereby summarized the amphibian-derived wound-healing-promoting peptides and their mechanism of action. Among these peptides, two peptides (tylotoin and TK-CATH) were characterized from salamanders, and twenty five peptides were characterized from frogs. These peptides generally have small sizes with 5–80 amino acid residues, nine peptides (tiger17, cathelicidin-NV, cathelicidin-DM, OM-LV20, brevinin-2Ta, brevinin-2PN, tylotoin, Bv8-AJ, and RL-QN15) have intramolecular disulfide bonds, seven peptides (temporin A, temporin B, esculentin-1a, tiger17, Pse-T2, DMS-PS2, FW-1, and FW-2) are amidated at the C-terminus, and the others are linear peptides without modifications. They all efficiently accelerated the healing of skin wounds or photodamage in mice or rats. They selectively promoted the proliferation and migration of keratinocytes and fibroblasts, recruited neutrophils and macrophages to wounds, and regulated the immune response of neutrophils and macrophages in wounds, which were essential for wound healing. Interestingly, MSI-1, Pse-T2, cathelicidin-DM, brevinin-2Ta, brevinin-2PN, and DMS-PS2 were just antimicrobial peptides, but they also significantly promoted the healing of infected wounds by clearing off bacteria. Considering the small size, high efficiency, and definite mechanism, amphibian-derived wound-healing-promoting peptides might be excellent candidates for developing novel wound-healing-promoting agents in future.