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miRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice

Authors Xu J, Bai S, Cao Y, Liu L, Fang Y, Du J, Luo L, Chen M, Shen B, Zhang Q

Received 24 December 2019

Accepted for publication 6 April 2020

Published 22 April 2020 Volume 2020:13 Pages 1259—1270


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Muthuswamy Balasubramanyam

Juan Xu,1,* Suwen Bai,2,* Yadi Cao,1 Lei Liu,1 Yang Fang,2 Juan Du,2 Li Luo,1 Mingwei Chen,1 Bing Shen,2 Qiu Zhang1

1Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, People’s Republic of China; 2School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Qiu Zhang
Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui 230022, People’s Republic of China
Tel/Fax +86-551-62923631
Bing Shen
Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230022, People’s Republic of China
Tel +86-551-65161132
Fax +86-551-65161126

Background: Patients with diabetic cutaneous ulcers experience financial burden and a lower quality of life and life expectancy. Endothelial progenitor cell (EPC)-derived exosomes facilitate skin wound healing by positively modulating vascular endothelial cell function. Exosomes play their important regulatory role through microRNA (miRNA). We explored the potential role and molecular mechanisms of miRNA in EPC-derived exosome healing of diabetic skin wounds.
Methods: Exosomes were isolated from the media of EPCs derived from mice bone marrow. High-throughput sequencing was used to detect the expression of exosome miRNA, and miRNA target genes were predicted using online databases. A diabetic mouse skin wound model was established, and wounds were treated with exosomes, miRNA-221-3p, or phosphate-buffered saline.
Results: Exosomes from EPCs accelerated skin wound healing in both control and diabetic mice. High-throughput sequencing showed that miRNA-221-3p was highly expressed in EPC-derived exosomes. Skin wound healing in control and diabetic mice was significantly enhanced by EPC-derived exosomes and miRNA-221-3p administration. Immunohistochemical analyses showed that EPC-derived exosomes and miRNA-221-3p increased protein expression levels of the angiogenesis-related factors VEGF, CD31 and cell proliferation marker Ki67. Bioinformatics analyses indicated that miRNA-221-3p may be involved in the AGE-RAGE signaling pathway in diabetic complications, cell cycle, and the p53 signaling pathway.
Conclusion: We concluded that miRNA-221-3p is one of the high-expressed miRNAs in EPC-derived exosomes and promoted skin wound healing in diabetic mice. The finding uncovers the molecular mechanism of EPC-derived exosomes and provides a potential novel approach to the clinical treatment of diabetic skin wounds.

Keywords: endothelial progenitor cells, exosome, diabetes, miRNA-221-3p, wound healing

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