1,25(OH)2D3 improves diabetic wound healing by modulating inflammation and promoting angiogenesis.

Yiming Ma, Yiting Gong, Ying Wu, Qiaofan Zhao, Ruyu Fu, Xiaoming Zhang, Ye Li, Xueyuan Zhi

The Journal of steroid biochemistry and molecular biology 2024 May

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Vitamin D was found to regulate inflammatory response and angiogenesis, which were often impaired in diabetic wound healing. This study aimed to investigate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on diabetic wound healing both in vivo and in vitro. Diabetes was induced by high-fat diet combined with streptozotocin. After four weeks of establishing diabetic mouse model, full-thickness excisional wounds were created on their dorsal skin. Then 1,25(OH)2D3 was administered via intraperitoneal injection for 14 consecutive days. Human umbilical vein endothelial cells (HUVECs) were cultured with normal glucose, high glucose, high glucose plus 1,25(OH)2D3. Cell proliferation, migration, tube formation, and expression levels of relevant pathway components were measured. Intervention with 1,25(OH)2D3 significantly increased wound closure rates of diabetic mice. During the inflammatory phase, 1,25(OH)2D3 alleviated excessive inflammation and promoted the transition of macrophages from M1 to M2 phenotype. Regarding vascular endothelial function, 1,25(OH)2D3 significantly up-regulated eNOS protein expression and inhibited Vcam-1 mRNA expression in diabetic mice (P < 0.05). As for angiogenesis, 1,25(OH)2D3 markedly increased CD31-positive area, the protein and mRNA expression of VEGF, VEGFR2, PDGF, and PDGFRβ, as well as the mRNA expression of Bfgf and Egfr (P < 0.05). In vitro, 1,25(OH)2D3 restored impaired cell proliferation, migration, and tube formation induced by high-glucose, and up-regulated expression of angiogenesis-related factors. These protective effects might be mediated through PI3K/AKT/HIF-1α pathway. These findings suggested that 1,25(OH)2D3 accelerated diabetic wound healing by modulating inflammation, restoring vascular endothelial dysfunction, and promoting angiogenesis. Copyright © 2024 Elsevier Ltd. All rights reserved.

Citation

Yiming Ma, Yiting Gong, Ying Wu, Qiaofan Zhao, Ruyu Fu, Xiaoming Zhang, Ye Li, Xueyuan Zhi. 1,25(OH)2D3 improves diabetic wound healing by modulating inflammation and promoting angiogenesis. The Journal of steroid biochemistry and molecular biology. 2024 May;239:106477