{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T17:09:51Z","timestamp":1788800991990,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008003","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["50531-2026"],"award-info":[{"award-number":["50531-2026"]}],"id":[{"id":"10.13039\/501100008003","id-type":"DOI","asserted-by":"publisher"}]},{"award":["50531-2026"],"award-info":[{"award-number":["50531-2026"]}],"id":[{"id":"https:\/\/ror.org\/023ktd084","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Basic Science Research Program","doi-asserted-by":"publisher","award":["RS-2023-00278034"],"award-info":[{"award-number":["RS-2023-00278034"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Current studies have elucidated the mechanisms of radiation-induced skin injury (RISI) and identified several medical countermeasures to reduce its severity. However, no treatment has yet proven effective in preventing or reversing radiation-induced skin fibrosis. Here, we show that radiation upregulates lipoprotein-associated phospholipase A2 (Lp-PLA2) expression and induces endothelial cell dysfunction, characterized by an increased DNA damage response and reduced tube-forming capacity and mitochondrial function. To define the role of Lp-PLA2 in the progression of RISI, we treated human dermal microvascular endothelial cells and the skin of SKH1 hairless mice with darapladib, a selective Lp-PLA2 inhibitor. In endothelial cells, darapladib attenuated radiation-induced cellular damage and suppressed endothelial-to-mesenchymal transition (EndoMT). In irradiated mouse skin, darapladib reduced radiation-induced inflammation, adipose tissue disruption, dermal thickness, and skin fibrosis. Notably, darapladib modulated macrophage polarization and inhibited radiation-induced macrophage infiltration in irradiated skin. These findings suggest that Lp-PLA2 inhibition may reveal potential targets for the treatment of RISI and other fibrotic skin diseases.<\/jats:p>","DOI":"10.3390\/biom16091292","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:30:02Z","timestamp":1788798602000},"page":"1292","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Darapladib Ameliorates Radiation-Induced Skin Injury and Fibrosis by Lipoprotein-Associated Phospholipase A2 Inhibition"],"prefix":"10.3390","volume":"16","author":[{"given":"Ji-Eun","family":"Park","sequence":"first","affiliation":[{"name":"Divisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"},{"name":"School of Radiological and Medical Sciences, University of Science and Technology (UST), 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4216-0857","authenticated-orcid":false,"given":"Narae","family":"Kim","sequence":"additional","affiliation":[{"name":"Divisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Ra","family":"Kim","sequence":"additional","affiliation":[{"name":"Divisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"Divisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3110-0384","authenticated-orcid":false,"given":"Yoon-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Divisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0307-3390","authenticated-orcid":false,"given":"Kwang Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Divisions of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea"},{"name":"School of Radiological and Medical Sciences, University of Science and Technology (UST), 75 Nowon-ro, Nowon-gu, Seoul 01812, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1742-4801.2005.00079.x","article-title":"Radiotherapy and wound healing","volume":"2","author":"Dormand","year":"2005","journal-title":"Int. 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