Inhibition of circulating exosomal microRNA-15a-3p accelerates diabetic wound repair

Abstract

Diabetic foot ulcers are a common complication of diabetes, and are usually incurable in the clinic. Exosomes (carriers that transfer endogenous molecules) from diabetic patients' blood have been demonstrated to suppress diabetic wound repair. In this study, we investigated the effects of circulating exosomal microRNA-15a-3p (miR-15a-3p) on diabetic wound repair. Exosomes were extracted from diabetic patients' blood, and were found to inhibit diabetic wound repair <i>in vitro</i> and <i>in vivo</i>. miR-15a-3p was upregulated in diabetic exosomes, and impaired wound healing. When miR-15a-3p was knocked down in diabetic exosomes, their negative effects were partially reversed both <i>in vitro</i> and <i>in vivo</i>. NADPH oxidase 5 (<i>NOX5</i>) was identified as a potential target of miR-15a-3p, and the inhibition of <i>NOX5</i> reduced the release of reactive oxygen species, thereby impairing the functionality of human umbilical vein endothelial cells. In summary, inhibition of circulating exosomal miR-15a-3p accelerated diabetic wound repair by activating <i>NOX5</i>, providing a novel therapeutic target for diabetic foot ulcer therapy.