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Given the expanding applications of NPWT, understanding its impact beyond open wounds is increasingly important. This study aimed to evaluate the biological responses of intact skin to negative\u2010pressure, specifically focusing on epithelial\u2010mesenchymal transition (EMT). The effects of negative\u2010pressure loading were assessed using an in\u00a0vitro model of non\u2010diabetic human keratinocytes and an in\u00a0vivo model of intact diabetic mouse skin. Human keratinocytes exposed to negative\u2010pressure exhibited increased expression of thrombospondin\u20101 (THBS1), transforming growth factor\u2010beta 1 (TGF\u2010\u03b21), plasminogen activator inhibitor\u20101 (PAI\u20101), and hypoxia\u2010inducible factor 1\u2010alpha (HIF\u20101\u03b1), alongside decreased epithelial markers and increased mesenchymal markers. These EMT\u2010related changes were mitigated by inhibiting the THBS1\u2010TGF\u2010\u03b21 interaction. Similarly, in diabetic mice, intermittent negative\u2010pressure loading applied to intact dorsal skin significantly increased THBS1 and TGF\u2010\u03b21 levels, resulting in epidermal and dermal thickening, and promoted hypoxic, prothrombotic and angiogenic responses, as evidenced by increased HIF\u20101\u03b1, PAI\u20101, fibrinogen and vascular endothelial growth factor expression. These findings suggest that negative\u2010pressure loading can induce EMT\u2010like responses and tissue remodelling in intact skin primarily via mechanisms involving the THBS1\u2010TGF\u2010\u03b21 signalling axis. This study expands the understanding of the biological influence of NPWT beyond traditional wound treatment applications, potentially informing future therapeutic considerations and safety guidelines.<\/jats:p>","DOI":"10.1111\/iwj.70859","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T06:24:38Z","timestamp":1773728678000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Negative\u2010Pressure Induces Epithelial\u2010Mesenchymal Transition via Thrombospondin\u20101 Upregulation in Intact Diabetic Skin"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7019-7740","authenticated-orcid":false,"given":"Toshifumi","family":"Yamashiro","sequence":"first","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery National Defense Medical College  Saitama 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