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

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, A...

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Autores principales:	Xu J, Bai S, Cao Y, Liu L, Fang Y, Du J, Luo L, Chen M, Shen B, Zhang Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	endothelial progenitor cells exosome diabetes mirna-221-3p wound healing Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/f4d87d9723b045968133e7e480fad933
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spelling	oai:doaj.org-article:f4d87d9723b045968133e7e480fad9332021-12-02T12:10:45ZmiRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice1178-7007https://doaj.org/article/f4d87d9723b045968133e7e480fad9332020-04-01T00:00:00Zhttps://www.dovepress.com/mirna-221-3p-in-endothelial-progenitor-cell-derived-exosomes-accelerat-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Juan 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 workCorrespondence: Qiu ZhangDepartment of Endocrinology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui 230022, People’s Republic of ChinaTel/Fax +86-551-62923631Email aynfmk@163.comBing ShenDepartment of Physiology, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230022, People’s Republic of ChinaTel +86-551-65161132Fax +86-551-65161126Email shenbing@ahmu.edu.cnBackground: 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 healingXu JBai SCao YLiu LFang YDu JLuo LChen MShen BZhang QDove Medical Pressarticleendothelial progenitor cellsexosomediabetesmirna-221-3pwound healingSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 1259-1270 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	endothelial progenitor cells exosome diabetes mirna-221-3p wound healing Specialties of internal medicine RC581-951
spellingShingle	endothelial progenitor cells exosome diabetes mirna-221-3p wound healing Specialties of internal medicine RC581-951 Xu J Bai S Cao Y Liu L Fang Y Du J Luo L Chen M Shen B Zhang Q miRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice
description	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 workCorrespondence: Qiu ZhangDepartment of Endocrinology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui 230022, People’s Republic of ChinaTel/Fax +86-551-62923631Email aynfmk@163.comBing ShenDepartment of Physiology, School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230022, People’s Republic of ChinaTel +86-551-65161132Fax +86-551-65161126Email shenbing@ahmu.edu.cnBackground: 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
format	article
author	Xu J Bai S Cao Y Liu L Fang Y Du J Luo L Chen M Shen B Zhang Q
author_facet	Xu J Bai S Cao Y Liu L Fang Y Du J Luo L Chen M Shen B Zhang Q
author_sort	Xu J
title	miRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice
title_short	miRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice
title_full	miRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice
title_fullStr	miRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice
title_full_unstemmed	miRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice
title_sort	mirna-221-3p in endothelial progenitor cell-derived exosomes accelerates skin wound healing in diabetic mice
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/f4d87d9723b045968133e7e480fad933
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miRNA-221-3p in Endothelial Progenitor Cell-Derived Exosomes Accelerates Skin Wound Healing in Diabetic Mice

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