{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:47:24Z","timestamp":1787323644352,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The pathogenesis of skin photodamage remains incompletely elucidated. Neutrophil extracellular traps (NETs) have been implicated in exacerbating skin photodamage. However, their precise mechanism requires further investigation. We detected NETs via immunofluorescence in skin tissues from patients with Actinic Dermatosis. In\u00a0vivo, an acute photodamage mouse model was established by using UVB irradiation. Mice were treated with GSK484 (PAD4 inhibitor) and subjected to RNA\u2010sequencing to explore the mechanism by which NETs promote inflammation and apoptosis. NETs content, malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activity were assessed. In\u00a0vitro, immortalized keratinocytes (HaCaT cells) were treated with NETs. Subsequently, cell viability, reactive oxygen species (ROS) levels, inflammatory cytokine release, apoptosis, SOD production, and MDA levels were measured. 25\u2010pass transmembrane protein (CCDC25) was knocked down to validate its role as a critical receptor for NETs in HaCaT cells. As a result, abundant NETs were present in the skin of Actinic Dermatosis patients. Injection of GSK484 significantly alleviated UVB\u2010induced skin damage, inflammation, and cell apoptosis in the mouse model. RNA\u2010sequencing analysis revealed that peptidyl\u2010arginine deiminase 4 (PAD4) deficiency inhibited UVB\u2010induced mitogen\u2010activated\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.sciencedirect.com\/topics\/biochemistry-genetics-and-molecular-biology\/protein-kinases\">protein kinase<\/jats:ext-link>\n                    (MAPK) activation. NETs treatment induced HaCaT cell apoptosis, suppressed cell viability, promoted inflammatory cytokine release, and disrupted redox homeostasis. NETs stimulation increased phospho\u2010Jun\u2010N\u2010terminal kinase (p\u2010JNK) activity. However, this activity was suppressed and cellular status was restored following CCDC25 knockdown. Collectively, NETs exacerbate skin photodamage by activating the p\u2010JNK\/JNK pathway via CCDC25, leading to HaCaT cell apoptosis, inhibition of cell viability, and the release of inflammatory cytokines.\n                  <\/jats:p>","DOI":"10.1111\/acel.70640","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T22:08:31Z","timestamp":1784844511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil Extracellular Traps Exacerbate UVB\u2010Induced Photodamage in HaCaT Cells and Mouse Skin via CCDC25\/MAPK Pathway"],"prefix":"10.1111","volume":"25","author":[{"given":"Yang","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Dermatology The First Affiliated Hospital of Chongqing Medical University  Chongqing 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