{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:37:03Z","timestamp":1788057423094,"version":"build-2784847793"},"reference-count":26,"publisher":"Scientific Scholar","content-domain":{"domain":["cytojournal.com"],"crossmark-restriction":true},"short-container-title":["Cytojournal"],"abstract":"\n Objective:<\/jats:title>\n Hypoxia-inducible factor 1 (HIF-1) signaling mediates multiple links of wound healing. Tissue hypoxia and dysregulation of HIF-1 signal play a crucial role in non-healing diabetic wounds. Previous studies have found that roxadustat (FG-4592) can promote epidermal stem cell proliferation by upregulating the HIF signaling pathway. This study aimed to investigate the role of roxadustat in the wound healing of diabetic mice.<\/jats:p>\n <\/jats:sec>\n \n Material and Methods:<\/jats:title>\n \n The study was divided into\n in vivo<\/jats:italic>\n and\n in vitro<\/jats:italic>\n experiments. In the\n in vivo<\/jats:italic>\n experiment, mice were categorized into three groups: control group, diabetes group, and diabetes + roxadustat group. Diabetic mice were injected intraperitoneally with roxadustat daily at a dose of 10 mg\/kg. Hematoxylin & eosin staining and Masson staining were employed to assess wound healing speed and quality. Immunohistochemical staining was used to detect HIF-1a and proliferating cell nuclear antigens. Western blot was conducted to examine markers associated with Notch1 signaling pathway activation (Notch Intracellular Domain [NICD]), keratinocyte differentiation, and angiogenesis. In the\n in vitro<\/jats:italic>\n experiment, HaCaT cells were divided into control (Glu 5.5 mM), high-glucose (Glu 30 mM), and high-glucose + drug (Glu 30 mM + FG-4592) groups, with a treatment concentration of FG-4592 set at 10 \u00b5M. Following 48 h of treatment period, protein was extracted for co-immunoprecipitation analysis to determine the interaction between HIF-1a and NICD, and fluorescence staining was conducted to assess their co-localization.\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n Roxadustat reversed the slow wound healing caused by diabetes and significantly improved the quality of healing (\n P<\/jats:italic>\n < 0.05). It upregulated the inhibited HIF-1 signaling in diabetic mice (\n P<\/jats:italic>\n < 0.05) and triggered cell proliferation. It downregulated the hyperactivated Notch1 signaling in diabetic mice (\n P<\/jats:italic>\n < 0.05) and induced keratinocyte dedifferentiation, which were both responsible for wound re-epithelialization. Roxadustat also reversed the downregulated expression of vascular endothelial growth factor and CD31 in diabetic mice (\n P<\/jats:italic>\n < 0.05) and accelerated the wound angiogenesis process.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Roxadustat shows potential as a therapeutic drug by promoting re-epithelialization and angiogenesis to bring vigor to the impaired diabetic wound.<\/jats:p>\n <\/jats:sec>","DOI":"10.25259\/cytojournal_235_2024","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T11:00:20Z","timestamp":1762254020000},"page":"90","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Roxadustat: A catalyst for diabetic wound healing through re-epithelialization and angiogenesis"],"prefix":"10.25259","volume":"22","author":[{"given":"Di","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Burn and Plastic Surgery, General Hospital 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