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mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype

Diabetic wounds are recalcitrant to healing. One of the important characteristics of diabetic trauma is impaired macrophage polarization with an excessive inflammatory response. Many studies have described the important regulatory roles of microRNAs (miRNAs) in macrophage differentiation and polariz...

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Autores principales: Hao, Yanhui, Yang, Leilei, Liu, Ying, Ye, Yumeng, Wang, Jiayu, Yu, Chao, Yan, Hua, Xing, Yuan, Jia, Zhaoqian, Hu, Cuicui, Zuo, Hongyan, Li, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724056/
https://www.ncbi.nlm.nih.gov/pubmed/34993211
http://dx.doi.org/10.3389/fmed.2021.775523
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author Hao, Yanhui
Yang, Leilei
Liu, Ying
Ye, Yumeng
Wang, Jiayu
Yu, Chao
Yan, Hua
Xing, Yuan
Jia, Zhaoqian
Hu, Cuicui
Zuo, Hongyan
Li, Yang
author_facet Hao, Yanhui
Yang, Leilei
Liu, Ying
Ye, Yumeng
Wang, Jiayu
Yu, Chao
Yan, Hua
Xing, Yuan
Jia, Zhaoqian
Hu, Cuicui
Zuo, Hongyan
Li, Yang
author_sort Hao, Yanhui
collection PubMed
description Diabetic wounds are recalcitrant to healing. One of the important characteristics of diabetic trauma is impaired macrophage polarization with an excessive inflammatory response. Many studies have described the important regulatory roles of microRNAs (miRNAs) in macrophage differentiation and polarization. However, the differentially expressed miRNAs involved in wound healing and their effects on diabetic wounds remain to be further explored. In this study, we first identified differentially expressed miRNAs in the inflammation, tissue formation and reconstruction phases in wound healing using Illumina sequencing and RT-qPCR techniques. Thereafter, the expression of musculus (mmu)-miR-145a-5p (“miR-145a-5p” for short) in excisional wounds of diabetic mice was identified. Finally, expression of miR-145a-5p was measured to determine its effects on macrophage polarization in murine RAW 264.7 macrophage cells and wound healing in diabetic mice. We identified differentially expressed miRNAs at different stages of wound healing, ten of which were further confirmed by RT-qPCR. Expression of miR-145a-5p in diabetic wounds was downregulated during the tissue formation stage. Furthermore, we observed that miR-145a-5p blocked M1 macrophage polarization while promoting M2 phenotype activation in vitro. Administration of miR-145a-5p mimics during initiation of the repair phase significantly accelerated wound healing in db/db diabetic mice. In conclusion, our findings suggest that rectifying macrophage function using miR-145a-5p overexpression accelerates diabetic chronic wound healing.
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spelling pubmed-87240562022-01-05 mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype Hao, Yanhui Yang, Leilei Liu, Ying Ye, Yumeng Wang, Jiayu Yu, Chao Yan, Hua Xing, Yuan Jia, Zhaoqian Hu, Cuicui Zuo, Hongyan Li, Yang Front Med (Lausanne) Medicine Diabetic wounds are recalcitrant to healing. One of the important characteristics of diabetic trauma is impaired macrophage polarization with an excessive inflammatory response. Many studies have described the important regulatory roles of microRNAs (miRNAs) in macrophage differentiation and polarization. However, the differentially expressed miRNAs involved in wound healing and their effects on diabetic wounds remain to be further explored. In this study, we first identified differentially expressed miRNAs in the inflammation, tissue formation and reconstruction phases in wound healing using Illumina sequencing and RT-qPCR techniques. Thereafter, the expression of musculus (mmu)-miR-145a-5p (“miR-145a-5p” for short) in excisional wounds of diabetic mice was identified. Finally, expression of miR-145a-5p was measured to determine its effects on macrophage polarization in murine RAW 264.7 macrophage cells and wound healing in diabetic mice. We identified differentially expressed miRNAs at different stages of wound healing, ten of which were further confirmed by RT-qPCR. Expression of miR-145a-5p in diabetic wounds was downregulated during the tissue formation stage. Furthermore, we observed that miR-145a-5p blocked M1 macrophage polarization while promoting M2 phenotype activation in vitro. Administration of miR-145a-5p mimics during initiation of the repair phase significantly accelerated wound healing in db/db diabetic mice. In conclusion, our findings suggest that rectifying macrophage function using miR-145a-5p overexpression accelerates diabetic chronic wound healing. Frontiers Media S.A. 2021-12-21 /pmc/articles/PMC8724056/ /pubmed/34993211 http://dx.doi.org/10.3389/fmed.2021.775523 Text en Copyright © 2021 Hao, Yang, Liu, Ye, Wang, Yu, Yan, Xing, Jia, Hu, Zuo and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Hao, Yanhui
Yang, Leilei
Liu, Ying
Ye, Yumeng
Wang, Jiayu
Yu, Chao
Yan, Hua
Xing, Yuan
Jia, Zhaoqian
Hu, Cuicui
Zuo, Hongyan
Li, Yang
mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype
title mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype
title_full mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype
title_fullStr mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype
title_full_unstemmed mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype
title_short mmu-miR-145a-5p Accelerates Diabetic Wound Healing by Promoting Macrophage Polarization Toward the M2 Phenotype
title_sort mmu-mir-145a-5p accelerates diabetic wound healing by promoting macrophage polarization toward the m2 phenotype
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724056/
https://www.ncbi.nlm.nih.gov/pubmed/34993211
http://dx.doi.org/10.3389/fmed.2021.775523
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