Neutrophil extracellular traps in wound healing

• Published in: Trends in pharmacological sciences (Regular ed.) 2024-11, Vol.45 (11), p.1033-1045
• Main Authors: Zhu, Zhanyong, Zhou, Shengzhi, Li, Sicheng, Gong, Song, Zhang, Qi
• Format: Article
• Language: English
• Subjects: Animals; Extracellular Traps; Humans; immune regulation; NET-targeted therapy; neutrophil extracellular traps; neutrophils; Neutrophils - metabolism; Wound Healing
• ISSN: 0165-6147; 1873-3735; 1873-3735
• DOI: 10.1016/j.tips.2024.09.007

Neutrophil extracellular traps (NETs) are crucial orchestrators in wound healing, exhibiting a dual nature by providing antimicrobial properties and mediating inflammation.The interactions between NETs and skin cells, such as fibroblasts, keratinocytes, and mesenchymal stem cells (MSCs), exhibit the multifaceted impact of NETs on wound healing.Imbalanced NET-related pathways, including NF-κB, PI3K-AKT, Hippo–YAP, and Wnt/β-catenin, may result in oxidative inflammation and hinder wound healing.Integrating immune markers like interleukin (IL)-1β, IL-6, and the NET-related biomarker citrullinated histone H3 (citH3) into predictive protocols can enhance the accuracy of wound healing prognosis.Therapeutic strategies targeting NETs through small molecule inhibitors, insulin, glycoproteins, MSCs, monoclonal antibodies, and gasotransmitters are effective in wound healing. Wound healing is a complex and orchestrated process that involves hemostasis, inflammation, proliferation, and tissue remodeling. Neutrophil extracellular traps (NETs) are intricate web-like structures released by neutrophils, comprising decondensed chromatin, myeloperoxidase (MPO), and neutrophil elastase (NE), which play vital roles in regulating neutrophil-mediated immune regulation. While NETs contribute to wound healing, excessive activation induced by dysregulated inflammation can hinder the healing process. Understanding the pivotal role of NETs in wound healing and tissue remodeling, as well as their intricate interactions within the wound microenvironment, presents opportunities for innovative wound healing strategies. In this review we discuss the process of NET formation, explore the interactions between NETs and skin cells, and examine therapeutic strategies targeting NETs and drug delivery platforms to accelerate wound healing. Additionally, we discuss current clinical investigations and research challenges towards advancing wound care practices. Wound healing is a complex and orchestrated process that involves hemostasis, inflammation, proliferation, and tissue remodeling. Neutrophil extracellular traps (NETs) are intricate web-like structures released by neutrophils, comprising decondensed chromatin, myeloperoxidase (MPO), and neutrophil elastase (NE), which play vital roles in regulating neutrophil-mediated immune regulation. While NETs contribute to wound healing, excessive activation induced by dysregulated inflammation can hinder the healing process. Understanding the pivotal r