{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:38:14Z","timestamp":1790116694045,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T00:00:00Z","timestamp":1719446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004772","name":"Natural Science Foundation of Ningxia Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004772","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabet Med"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>The objective was to investigate the specific role and the regulatory mechanism of vascular endothelial growth factor (VEGF) during wound healing in diabetic foot ulcer (DFU).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Streptozotocin\u2010induced diabetic rats were used to establish a DFU animal model. VEGF and Axitinib (a specific inhibitor of VEGFR) were used for treatment in\u00a0vivo. The wounds at different time points were imaged and histological analysis of the wounds were performed by haematoxylin and eosin (H&amp;E) staining and Masson's trichrome staining. Immunohistochemical staining was conducted to examine CD31 and eNOS expression in the wounds. Immunofluorescence assay and quantitative real\u2010time PCR were performed to examine macrophage markers. In addition, THP\u20101 was differentiated to macrophages, and then treated with interleukin (IL)\u20104 to induce M2 macrophages, followed by VEGF treatment. The conditional medium (CM) from VEGF\u2010mediated macrophages were collected to culture human dermal fibroblasts (HDFs). Cell viability and migration were measured by Cell Counting Kit (CCK)\u20108, wound\u2010healing and Transwell assays, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>VEGF treatment remarkably accelerated wound healing of DFU rats. VEGF promoted collagen deposition and elevated CD31 and eNOS expression, confirming the pro\u2010angiogenesis of VEGF around diabetic wound in rats. Meanwhile, VEGF restricted pro\u2010inflammatory cytokines and increased F4\/80 and CD206 expression, highlighting the activated macrophages and enhanced M2 macrophages following VEGF treatment in diabetic wounds of DFU rats. However, Axitinib exerted an opposite function to VEGF in DFU rats. Moreover, VEGF directly promoted macrophage polarization toward M2 phenotype in\u00a0vitro, and the CM from VEGF\u2010mediated M2 macrophages markedly promoted HDFs proliferation, migration and collagen deposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>VEGF might accelerate the wound healing of DFU through promoting M2 macrophage polarization and fibroblast migration.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dme.15388","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T12:55:01Z","timestamp":1719492901000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Vascular endothelial growth factor accelerates healing of foot ulcers in diabetic rats via promoting <scp>M2<\/scp> macrophage polarization"],"prefix":"10.1111","volume":"41","author":[{"given":"Fei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Hand, Foot and Ankle Surgery General Hospital of Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianrui","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology General Hospital of Ningxia Medical University  Yinchuan Ningxia China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Burn and Plastic Surgery General Hospital of Ningxia Medical University  Yinchuan Ningxia 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