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Despite advances in wound healing approaches, optimal management strategies are lacking, partly due to an incomplete understanding of the complex pathophysiology of this process. Here we show that Ang2, a previously known ligand for the Tie2 receptor, also binds to fibroblast growth factor receptor 2 (FGFR2) independently of Tie2 and attenuates FGF\/FGFR2 signaling in endothelial cells. Functionally, Ang2 inhibits endothelial cell migration induced by FGF. In mouse, topical Ang2 delays the healing of skin wounds, associated with reduced wound angiogenesis and recruitment of mesenchymal-type cells. Additionally, topical AMG386, a blocker of Ang1\/Ang2 binding to Tie2 and systemic REGN910, a blocker of Ang2 binding to Tie2, accelerate wound repair, associated with increased wound angiogenesis and recruitment of inflammatory cells. These results identify the tyrosine kinase FGFR2 as a previously unrecognized Ang2 receptor, explaining some of the context-dependent functions of Ang2 in endothelial cells. Since Ang2 is induced in cutaneous wounds and endogenous FGF\/FGFR2 is essential for wound repair, Ang2 blockade holds promise as a new evidence-based therapeutic option to promote wound repair.<\/jats:p>","DOI":"10.1007\/s10456-025-09988-2","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T17:59:45Z","timestamp":1754416785000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Angiopoietin-2 binds to FGFR2, inhibits FGF-FGFR2 signaling, and delays cutaneous wound healing by inhibiting wound angiogenesis"],"prefix":"10.1007","volume":"28","author":[{"given":"Minji","family":"Sim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetaka","family":"Ohnuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Durell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haydar","family":"Bulut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"Dyba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey G.","family":"Tarasov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Tosato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"issue":"7193","key":"9988_CR1","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/nature07039","volume":"453","author":"GC Gurtner","year":"2008","unstructured":"Gurtner GC, Werner S, Barrandon Y, Longaker MT (2008) Wound repair and regeneration. 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