Kui Xiao , Sisi Wang , Gang Li , Wenxin Chen , Bin Chen , Xiaojian Li
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引用次数: 0
Abstract
Background
Diabetic wounds are a common complication of diabetes, with alarming disability and mortality rates. Ferroptosis plays an essential role in the occurrence and development of diabetes mellitus and its complications, suggesting that mitigating ferroptosis can be used as a potential therapeutic strategy. Resveratrol (RSV) can promote the angiogenesis of diabetic wounds, but its molecular mechanism is unclear, and RSV has a role in regulating ferroptosis. Therefore, we speculated that RSV could promote the angiogenesis of diabetic wounds and accelerate wound healing by regulating ferroptosis.
Methods
In this study, we investigated the effects of RSV on human umbilical vein endothelial cells (HUVECs) treated with advanced glycation end-products (AGEs), focusing primarily on cell proliferation and markers associated with ferroptosis. The methods employed included the CCK-8 assay for cell proliferation, ROS determination, Fe²⁺ measurement, scratch and tube formation assays, and transcriptome analysis. To evaluate the effectiveness of RSV in promoting wound healing, we established a type 2 diabetes rat model and created a skin injury model. Wound healing rates were assessed, and tissue samples were analyzed using hematoxylin and eosin (H&E) staining, immunohistochemistry, immunofluorescence, and Western blotting. Additionally, levels of glutathione (GSH) and malondialdehyde (MDA) were measured to evaluate oxidative stress and lipid peroxidation.
Result
Upon treatment of HUVECs with AGEs, we observed a decrease in cell viability and induction of ferroptosis. RSV can alleviate ferroptosis in AGEs-treated HUVECs. Further investigation through transcriptome analysis and Western blotting revealed that RSV alleviates ferroptosis in AGE-treated HUVECs by modulating the activity of nuclear factor erythroid 2-related factor 2 (Nrf2). In vivo experiments using a diabetic rat skin injury model confirmed that both RSV and Ferrostatin-1 (Fer-1) enhance wound healing and angiogenesis. This effect was associated with the regulation of ferroptosis marker proteins including GPX4, SLC7A11, and ACSL4. Additionally, in the diabetic rat groups treated with RSV and Fer-1, we noted increased expression of Nrf2, vascular endothelial growth factor (VEGF), and CD31 proteins compared to the diabetic rat control group.
Conclusion
In diabetic wounds, AGEs can lead to ferroptosis in HUVECs. RSV can inhibit AGE-induced ferroptosis in HUVECs, further promoting angiogenesis in diabetic wounds, and ultimately accelerating wound healing.
期刊介绍：
Burns aims to foster the exchange of information among all engaged in preventing and treating the effects of burns. The journal focuses on clinical, scientific and social aspects of these injuries and covers the prevention of the injury, the epidemiology of such injuries and all aspects of treatment including development of new techniques and technologies and verification of existing ones. Regular features include clinical and scientific papers, state of the art reviews and descriptions of burn-care in practice.
Topics covered by Burns include: the effects of smoke on man and animals, their tissues and cells; the responses to and treatment of patients and animals with chemical injuries to the skin; the biological and clinical effects of cold injuries; surgical techniques which are, or may be relevant to the treatment of burned patients during the acute or reconstructive phase following injury; well controlled laboratory studies of the effectiveness of anti-microbial agents on infection and new materials on scarring and healing; inflammatory responses to injury, effectiveness of related agents and other compounds used to modify the physiological and cellular responses to the injury; experimental studies of burns and the outcome of burn wound healing; regenerative medicine concerning the skin.
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