{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:16:10Z","timestamp":1788354970875,"version":"build-2803163510"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Wound Repair Regeneration"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Delayed re\u2010epithelialisation is a key feature of chronic and recurrent cutaneous wounds, but the metabolic mechanisms that coordinate keratinocyte migration and epidermal barrier restoration remain incompletely defined. Here, we investigated whether NUCB2\/Nesfatin\u20101 regulates keratinocyte\u2010driven wound repair through cholesterol biosynthesis. Transcriptomic profiling revealed coordinated downregulation of cholesterol biosynthetic genes in NUCB2\u2010deficient keratinocytes. Concurrently, gene signatures associated with cell motility and epithelial plasticity were also suppressed. Functionally, NUCB2 depletion impaired CCK\u20108\u2010based metabolic\/proliferative activity, scratch\u2010wound closure, Transwell migration and epithelial marker expression, whereas exogenous Nesfatin\u20101 partially restored these defects. Mechanistic analyses showed that NUCB2\/Nesfatin\u20101 enhanced mTORC1 downstream signalling, increased nuclear SREBP2 abundance and HMGCR expression, and promoted intracellular cholesterol accumulation. Cholesterol supplementation or HMGCR overexpression partially restored cholesterol availability and migratory capacity in NUCB2\u2010deficient keratinocytes, whereas rapamycin attenuated Nesfatin\u20101\u2010associated SREBP2\u2013HMGCR induction, cholesterol accumulation and migration. In a murine full\u2010thickness excisional wound model, local Nesfatin\u20101 administration accelerated wound closure and enhanced early re\u2010epithelialisation, accompanied by increased SREBP2 and HMGCR expression at the wound\u2010edge epidermis. Complementary local Nucb2 silencing delayed wound closure. These findings define a NUCB2\/Nesfatin\u20101\u2013mTORC1 downstream signalling\u2013SREBP2\u2013HMGCR axis that supports cholesterol\u2010dependent keratinocyte migration and epidermal repair.<\/jats:p>","DOI":"10.1111\/wrr.70210","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:27:47Z","timestamp":1788352067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>NUCB2<\/scp>\n                    \/Nesfatin\u20101 Couples Cholesterol Biosynthesis to Keratinocyte Migration to Accelerate Re\u2010Epithelialisation in Cutaneous Wound Repair"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8530-0273","authenticated-orcid":false,"given":"Jingwen","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Immunology College of Xiangya Basic Medical Sciences, Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4755-775X","authenticated-orcid":false,"given":"Liang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pathology Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children's Medical Center for South Central Region  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0948-0277","authenticated-orcid":false,"given":"Kangtao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General and Vascular Surgery Xiangya Hospital, Central South University  Changsha China"},{"name":"National Clinical Research Center for Geriatric Disease (Xiangya Hospital)  Changsha China"},{"name":"Clinical Research Center for Vascular Intervention in Hunan Province, Xiangya Hospital, Central South 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