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Impaired wound healing is associated with increased inflammation and poor angiogenesis in diabetes patients. Here, we demonstrate that topical administration of a secreted recombinant protein (Meteorin-like [Metrnl]) accelerates wound epithelialization and angiogenesis in mice. We observed a significant increase in Metrnl expression during physiological wound healing; however, its expression remained low during diabetic wound healing. Functionally, the recombinant protein Metrnl significantly accelerated wound closure in normal and diabetic mice models including db\/db, high-fat diet\/streptozotocin (HFD\/STZ), and STZ mice. Mechanistically, keratinocytes secrete quantities of Metrnl to promote angiogenesis; increase endothelial cell proliferation, migration, and tube formation; and enhance macrophage polarization to the M2 type. Meanwhile, M2 macrophages secrete Metrnl to further stimulate angiogenesis. Moreover, the keratinocyte- and macrophage-produced cytokine Metrnl drives postinjury angiogenesis and reepithelialization through activation of AKT phosphorylation (S473) in a KIT receptor tyrosine kinase (c-Kit)\u2013dependent manner. In conclusion, our study suggests that Metrnl has a biological effect in accelerating wound closure through c-Kit\u2013dependent angiogenesis and epithelialization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                  <\/jats:sec>","DOI":"10.2337\/db23-0173","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T14:05:16Z","timestamp":1694181916000},"page":"1692-1706","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":40,"title":["Accelerating Wound Closure With Metrnl in Normal and Diabetic Mouse Skin"],"prefix":"10.2337","volume":"72","author":[{"given":"Lingyu","family":"Song","sequence":"first","affiliation":[{"name":"1Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China"},{"name":"2Department of Gastroenterology, Affiliated Hospital of Guizhou Medical 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Song","sequence":"additional","affiliation":[{"name":"6School of Nursing, Southwest Medical University, Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Hu","sequence":"additional","affiliation":[{"name":"6School of Nursing, Southwest Medical University, Luzhou, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xiao","sequence":"additional","affiliation":[{"name":"1Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingjun","family":"Shi","sequence":"additional","affiliation":[{"name":"1Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Liu","sequence":"additional","affiliation":[{"name":"1Department of Pathophysiology, Guizhou Medical University, Guiyang, Guizhou, 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