☆ 4.4 Article

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

DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY (2020)

Journal

DIABETES METABOLIC SYNDROME AND OBESITY-TARGETS AND THERAPY

Volume 13, Issue -, Pages 1259-1270

Publisher

DOVE MEDICAL PRESS LTD

DOI: 10.2147/DMSO.S243549

Keywords

endothelial progenitor cells; exosome; diabetes; miRNA-221-3p; wound healing

Funding

National Natural Science Foundation of China [81970703, 81570403, U1732157]

Ask authors/readers for more resources

Protocol

Community support

Reagent

Community support

Abstract

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.

Authors

I am an author on this paper

Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.4

Not enough ratings

Secondary Ratings

Novelty

Significance

Scientific rigor

Rate this paper

Exosomes from tannic acid-stimulated macrophages accelerate wound healing through miR-221-3p mediated fibroblasts migration by targeting CDKN1b

Xu Song, Yaqin Chen, Xiangxiu Chen, Xinghong Zhao, Yuanfeng Zou, Lixia Li, Xun Zhou, Mingyue Li, Dongmei Zhang, Gang Ye, Renyong Jia, Zhongqiong Yin

Summary: Tannic acid (TA) has been traditionally used for treating traumatic bleeding in China and has been shown to accelerate wound healing in rats. This study aims to uncover the mechanism behind TA's promotion of wound healing. Results show that TA enhances macrophage growth and inhibits the release of inflammatory cytokines by inhibiting the NF-κB/JNK pathway. TA also activates the Erk1/2 pathway, leading to increased expressions of growth factors and promoted fibroblast migration. Additionally, TA stimulates macrophages to secrete exosomes enriched in miR-221-3p, which enter fibroblasts and bind to the CDKN1b gene, promoting fibroblast migration. This study provides new insights into TA's acceleration of wound healing in the inflammatory and proliferative phases.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2023)