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Aging
05 21, 2020;12 (10): 8968-8986.

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

Yuan Xiong, Lang Chen, Tao Yu, Chenchen Yan, Wu Zhou, Faqi Cao, Xiaomeng You, Yingqi Zhang, Yun Sun, Jing Liu, Hang Xue, Yiqiang Hu, Dong Chen, Bobin Mi, Guohui Liu
Author Information
  1. Yuan Xiong: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  2. Lang Chen: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  3. Tao Yu: Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
  4. Chenchen Yan: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  5. Wu Zhou: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  6. Faqi Cao: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  7. Xiaomeng You: Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02125, USA.
  8. Yingqi Zhang: Department of Orthopedic Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
  9. Yun Sun: Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  10. Jing Liu: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  11. Hang Xue: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  12. Yiqiang Hu: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  13. Dong Chen: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  14. Bobin Mi: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  15. Guohui Liu: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
PMID: 32439831 DOI: 10.18632/aging.103143

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 and . 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 and . NADPH oxidase 5 () was identified as a potential target of miR-15a-3p, and the inhibition of 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 , providing a novel therapeutic target for diabetic foot ulcer therapy.

Keywords

NADPH oxidase 5 diabetic foot ulcer exosome microRNA-15a-3p wound repair

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MeSH Term

Animals
Diabetes Complications
Disease Models, Animal
Exosomes
Gene Knockdown Techniques
Human Umbilical Vein Endothelial Cells
Humans
Male
Mice, Inbred C57BL
MicroRNAs
Wound Healing

Chemicals

MIRN15 microRNA, human
MicroRNAs
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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