Journal
AGING-US
Volume 12, Issue 10, Pages 8968-8986Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.103143
Keywords
microRNA-15a-3p; exosome; diabetic foot ulcer; wound repair; NADPH oxidase 5
Categories
Funding
- National Science Foundation of China [81772345]
- National Health Commission of the People's Republic of China [ZX-01-018, ZX-01-C2016153]
- Ministry of Science and Technology of the People's Republic of China [2018YFC2001502, 2018YFB1105705]
- Health Commission of Hubei Province [WJ2019Z009]
- Wuhan Science and Technology Bureau [2017060201010192]
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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 in vitro and in vivo. 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 in vitro and in vivo. NADPH oxidase 5 (NOX5) was identified as a potential target of miR-15a-3p, and the inhibition of NOX5 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 NOX5, providing a novel therapeutic target for diabetic foot ulcer therapy.
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