Journal Article

The Multifunctional Peptide AP10W Enhances Skin Wound Healing Through Macrophage Reprogramming and Angiogenesis

Wu, Fei, Liu, Bojian, Zhang, Peng, Xuan, Cuiling, Gao, Zhiqin, Liu, Zixuan

2026

Overview

Skin wound healing is a complex and highly coordinated biological process involving inflammation, cell migration and proliferation, angiogenesis, extracellular matrix remodeling and tissue regeneration. While the zebrafish-derived antimicrobial peptide AP10W exhibits broad-spectrum antimicrobial properties, its potential in tissue repair remains unexplored. Herein, we demonstrate that AP10W possesses intrinsic wound-healing capabilities, providing a preliminary investigation into its underlying mechanisms. In this study, using a full-thickness murine wound model and in vitro cell-based assays to evaluate the effects of AP10W on fibroblasts, keratinocytes, endothelial cells, and macrophages, we found that AP10W significantly promoted fibroblast and keratinocyte migration and proliferation. Furthermore, it enhanced endothelial cell motility, survival, and tube formation, while upregulating key pro-angiogenic factors, including Vascular endothelial growth factor A (VEGFA), Platelet-derived growth factor (PDGF), and Fibroblast growth factor 2 (FGF2). Concurrently, AP10W drove macrophage reprogramming from a pro-inflammatory M1 phenotype toward a pro-healing M2 state, as evidenced by upregulated Arginase-1 (Arg-1) and Interleukin-10 (Il-10) expression, alongside attenuated Tumor necrosis factor-alpha (Tnf-α), Interleukin-1 beta (Il-1β), Interleukin-6 (Il-6), and Inducible nitric oxide synthase (iNOS) levels. In vivo, the topical application of AP10W accelerated wound closure, markedly improving re-epithelialization, collagen deposition, vascularization, tissue perfusion, and skin appendage regeneration. Preliminary mechanistic studies revealed that AP10W increased YAP expression and nuclear translocation; conversely, the pharmacological inhibition of YAP significantly abrogated these pro-healing effects. Collectively, our findings identify AP10W as a multifunctional peptide with potent wound-healing properties, positioning it as a promising candidate for wound therapy.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Angiogenesis / Angiogenesis - drug effects / Animals / Antimicrobial agents / antimicrobial peptide AP10W / Antimicrobial peptides / Antimicrobial Peptides - pharmacology / Arginase / Bacteria / Care and treatment / Cell adhesion & migration / Cell culture / Cell growth / Cell Movement - drug effects / Cell Proliferation - drug effects / Cell survival / Cellular Reprogramming - drug effects / Collagen / Endothelial cells / Endothelium / Extracellular matrix / Fibroblast growth factor 2 / Fibroblasts / Fibroblasts - drug effects / Fibroblasts - metabolism / Growth factors / Humans / Inflammation / Interleukin 1 / Interleukin 10 / Interleukin 6 / Interleukins / Keratinocytes / Keratinocytes - drug effects / Keratinocytes - metabolism / Leukocyte migration / macrophage reprogramming / Macrophages / Macrophages - drug effects / Macrophages - metabolism / Mice / Neovascularization, Physiologic - drug effects / Nitric oxide / Nitric-oxide synthase / Nuclear transport / Oxidative stress / Pathogens / Peptides / Phenotypes / Platelet-derived growth factor / Skin / Skin - drug effects / Skin - metabolism / Tissue engineering / Topical application / Tumor necrosis factor-α / Vascular endothelial growth factor / Vascularization / Wound healing / Wound Healing - drug effects / Wounds and injuries / YAP signaling / YAP-Signaling Proteins / Yes-associated protein