Acidic fibroblast growth factor inhibits reactive oxygen species-induced epithelial–mesenchymal transdifferentiation in vascular endothelial cells via the miR-155-5p/SIRT1/Nrf2/HO-1 pathway to promote wound healing in diabetic mice

Abstract

Background: Diabetic chronic wounds are among the most common and serious complications of diabetes and are associated with significant morbidity and mortality. Endothelial-to-mesenchymal transition (EndMT) is a specific pathological state in which endothelial cells are transformed into mesenchymal cells in response to various stimuli, such as high glucose levels and high oxidative stress. Acidic fibroblast growth factor (aFGF), which is a member of the fibroblast growth factor family, possesses strong antioxidant properties and can promote the differentiation of mesenchymal stem cells into angiogenic cells. Therefore, we investigated the role of aFGF in EndMT in diabetic wounds and analysed the underlying mechanisms. Methods: A diabetic mouse model was used to verify the effect of aFGF on wound healing, and the effect of aFGF on vascular endothelial cells in a high-glucose environment was examined in vitro. We examined the expression of miR-155-5p in a high-glucose environment and the miR-155 downstream target gene SIRT1 by luciferase reporter assays. Results: aFGF promoted wound closure and neovascularization in a mouse model of type 2 diabetes. In vitro, aFGF inhibited the production of total and mitochondrial reactive oxygen species (ROS) in vascular endothelial cells and alleviated epithelial–mesenchymal transdifferentiation in a high-glucose environment. Mechanistically, aFGF promoted the expression of SIRT1 and the downstream targets Nrf2 and HO-1 by negatively regulating miR-155-5p, thereby reducing ROS generation. Conclusions: In conclusion, our results suggest that aFGF inhibits ROS-induced epithelial–mesenchymal transdifferentiation in diabetic vascular endothelial cells via the miR-155-5p/SIRT1/Nrf2/HO-1 axis, thereby promoting wound healing.

Keywords

EndMT / Acidic fibroblast growth factor / Reactive oxygen species / Chronic wounds / Wound healing / Diabetic wound / Fibroblast

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