Research Paper|Volume 12, Issue 10|pp 8968—8986

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

Yuan Xiong¹, Lang Chen¹, Tao Yu², Chenchen Yan¹, Wu Zhou¹, Faqi Cao¹, Xiaomeng You³, Yingqi Zhang², Yun Sun⁴, Jing Liu¹, Hang Xue¹, Yiqiang Hu¹, Dong Chen¹, Bobin Mi¹, Guohui Liu¹

¹Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
²Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
³Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02125, USA
⁴Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

* Equal contribution

Received: January 24, 2020Accepted: March 31, 2020Published: May 21, 2020

https://doi.org/10.18632/aging.103143

Copyright © 2020 Xiong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 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.