Neutrophil extracellular traps (NETs) amplify UV-induced skin damage through a CCDC25-mediated signaling pathway that triggers keratinocyte death and oxidative stress. Blocking NET formation with PAD4 inhibition protects against photodamage in both cellular and animal models, identifying a potential intervention target for UV-related skin aging and actinic dermatosis.
Key Points
- NETs bind CCDC25 receptors, activating p-JNK pathway in skin cells
- PAD4 inhibition reduces NET formation and prevents UVB-induced damage
- NETs disrupt cellular redox balance, triggering apoptosis and inflammation
Longevity Analysis
UV exposure triggers an inflammatory cascade mediated by immune cells that extends far beyond direct DNA damage to skin cells. The identification of NETs as a pathogenic intermediary reveals that controlling this secondary inflammatory response—through mechanisms like PAD4 inhibition—may be as critical as physical photoprotection. Since immune activation, oxidative stress, and cellular death accelerate tissue aging, interventions that prevent NET formation could address a fundamental mechanism linking environmental insult to photoaging and skin disease progression.
Original published by Wiley Aging Cell, by Yang Zou, Junzhi Li, Yuting Peng, Rui Hu, Ruolin Li, Aijun Chen .