Maggot excretions/secretions promote diabetic wound angiogenesis via miR18a/19a-TSP-1 axis

Aims: The impaired angiogenesis is one of the main factors affecting the healing of diabetic foot ulcer (DFU) wounds. Maggot debridement therapy (MDT) promotes granulation tissue growth and angiogenesis during DFU wound healing. Non-coding microRNAs can also promote local angiogenesis in DFU wounds by regulating wound repairing related gene expression. The purpose of this study was to investigate the mechanism of microRNAs in MDT promoting DFU wound angiogenesis. Methods: In this study, we applied MDT to treat DFU wound tissue and detect the expression of the miR-17-92 cluster. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were treated with maggot excretions/secretions (ES), the miR-17-92 cluster and the predicted target gene expression were measured. Tube formation assay and cell scratch assay were performed when inhibition of miR-18a/19a or overexpression of thrombospondin-1 (TSP-1) were used in this study. Results: miR-18a/19a transcription significantly up-regulated and TSP-1 expression down-regulated in patients wound tissue and in HUVECs. Inhibition of miR-18a/19a or overexpression of TSP-1 partially blocked the migration and tube formation ability stimulated by ES. Conclusion: Targeted activation of miR-18a/19a transcription levels and subsequent regulation of TSP-1 expression may be a novel therapeutic strategy for DFU. (C) 2020 Elsevier B.V. All rights reserved.