The Antimicrobial Peptide Esculentin-1a(1–21)NH₂ Stimulates Wound Healing by Promoting Angiogenesis through the PI3K/AKT Pathway

Abstract

Delayed wound healing is a persistent medical problem mainly caused by decreased angiogenesis. Esculentin-1a(1–21)NH₂ [Esc-1a(1–21)NH₂], has broad-spectrum antibacterial properties which comes from frog skins. It has shown promise as a treatment for wound healing. However, its effects on angiogenesis as well as the mechanism by which esc-1a(1–21)NH₂ enhanced wound healing remained unclear. In this study, we analyzed the structural properties and biocompatibility of esc-1a(1–21)NH₂ and evaluated its effect on wound closure using a full-thickness excision model in mice. Our results showed that esc-1a(1–21)NH₂ significantly accelerated wound healing by increasing collagen deposition and angiogenesis, characterized by elevated expression levels of platelet, endothelial cell adhesion molecule-1 (CD31) and proliferating cell nuclear antigen (PCNA). Furthermore, the angiogenic activity of esc-1a(1–21)NH₂ was confirmed in vitro by various assays. Esc-1a(1–21)NH₂ significantly promoted cell migration and cell proliferation in human umbilical vein vascular endothelial cells (HUVECs) via activation of the phosphatidylinositol 3′-kinase (PI3K)/protein kinase B (AKT) pathway, and upregulated the expression of CD31 at both mRNA and protein levels. The effect of esc-1a(1–21)NH₂ on angiogenesis was diminished by LY294002, a PI3K pathway inhibitor. Taken together, this study demonstrates that esc-1a(1–21)NH₂ accelerates wound closure in mice by promoting angiogenesis via the PI3K/AKT signaling pathway, suggesting its effective application in the treatment of wound healing.