The role of FGF-21 in promoting diabetic wound healing by modulating high glucose-induced inflammation

Highlights•FGF-21 treatment restored endothelial cell proliferation, migration, and tube-forming ability in vitro, which had been impaired due to hyperglycemia damage.•In both in vivo and in vitro experiments, FGF-21 attenuated the inflammatory response induced by high glucose in wounds and skin cells.•The wound-healing and angiogensis-promoting effects of FGF-21 treatment were comparable to those of VEGF in diabetic wounds.AbstractBackgroundWound healing is a complex biological process that can be impaired in individuals with diabetes. Diabetic wounds are a serious complication of diabetes that require promoting diagnosis and effective treatment. FGF-21, a member of the endocrine FGF factors family, has caught the spotlight in the treatment of diabetes for its beneficial effects on accelerating human glucose uptake and fat catabolism. However, the therapeutic efficacy of FGF-21 in promoting diabetic wounds remains unknown. This study aims to evaluate the therapeutic potential of FGF-21 in promoting diabetic wound healing.Methodswe investigated the effects of FGF-21 on wound healing related-cells under high-glucose conditions using various assays such as CCK8, scratch assay, flow cytometry analysis, endothelial tube-formation assay, and transmission electron microscopy. Furthermore, we used db/db mice to verify the healing-promoting therapeutic effects of FGF-21 on diabetic wounds. We also conducted qRT-PCR, Western blot, and immunofluorescence staining analyses to elucidate the underlying mechanism.ResultOur results indicate that FGF-21 treatment restored hyperglycemic damage on endothelial cell proliferation, migration, and tube-forming ability. It also reduced endothelial cell death rates under high-glucose conditions. TEM analysis showed that FGF-21 treatment effectively restored mitochondrial damage and morphological changes in endothelial cells caused by glucose. Additionally, qRT-PCR and Western blot analysis indicated that FGF-21 treatment restored inflammatory responses caused by hyperglycemic damage. Animal experiments confirmed these findings, suggesting that FGF-21 may be a promising candidate for the treatment of non-healing diabetic wounds due to its effectiveness in stimulating angiogenesis and anti-inflammatory function.ConclusionOur study provides evidence that FGF-21 is an essential regulator of wound-related cells under high-glucose conditions and has the potential to be a novel therapeutic target for accelerating diabetic wound healing.