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Hydrogen Peroxide-Induced Senescence Reduces the Wound Healing-Promoting Effects of Mesenchymal Stem Cell-Derived Exosomes Partially via miR-146a

Mesenchymal stem cells (MSCs) have beneficial effects on wound healing. MSCs function through direct cell-cell communication or indirectly through paracrine secretion of exosomes. Here, we found that MSC-derived exosomes had pro-wound healing effects via promotion of angiogenesis; however, this prom...

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Autores principales: Xu, Meiqian, Su, Xiaodong, Xiao, Xian, Yu, Hongliang, Li, Xiaoxia, Keating, Armand, Wang, Shihua, Zhao, Robert Chunhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: JKL International LLC 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801275/
https://www.ncbi.nlm.nih.gov/pubmed/33532131
http://dx.doi.org/10.14336/AD.2020.0624
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author Xu, Meiqian
Su, Xiaodong
Xiao, Xian
Yu, Hongliang
Li, Xiaoxia
Keating, Armand
Wang, Shihua
Zhao, Robert Chunhua
author_facet Xu, Meiqian
Su, Xiaodong
Xiao, Xian
Yu, Hongliang
Li, Xiaoxia
Keating, Armand
Wang, Shihua
Zhao, Robert Chunhua
author_sort Xu, Meiqian
collection PubMed
description Mesenchymal stem cells (MSCs) have beneficial effects on wound healing. MSCs function through direct cell-cell communication or indirectly through paracrine secretion of exosomes. Here, we found that MSC-derived exosomes had pro-wound healing effects via promotion of angiogenesis; however, this promoting effect was significantly reduced when senescence was induced in parental MSCs by hydrogen peroxide (H(2)O(2)). Further experiments showed that decreased miR-146a expression in exosomes derived from senescent MSCs (s-exo) contributed to these findings. In vitro, the pro-angiogenic effect of s-exo on tube formation in human umbilical vein endothelial cells was significantly reduced compared with that of exosomes derived from control MSCs (c-exo). In vivo, higher tube numbers and longer tube lengths were observed in the c-exo group compared with the s-exo group. Using microarray analysis, we found that miR-146a level in s-exo was lower than that in c-exo. Knockdown of miR-146a in c-exo decreased its capacity to promote angiogenesis, and overexpression of miR-146a in s-exo partially rescued its impaired pro-angiogenic capacity, thereby confirming that downregulation of miR-146a contributed to the reduced pro-wound healing capacity of s-exo. Our study is the first to demonstrate that cell senescence induced by H(2)O(2) alters the pro-angiogenic ability of exosomes by modulating the expression of exosomal miRNAs, especially miR-146a, thus providing new insights into the correlation between parental cell state and exosome content and function.
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spelling pubmed-78012752021-02-01 Hydrogen Peroxide-Induced Senescence Reduces the Wound Healing-Promoting Effects of Mesenchymal Stem Cell-Derived Exosomes Partially via miR-146a Xu, Meiqian Su, Xiaodong Xiao, Xian Yu, Hongliang Li, Xiaoxia Keating, Armand Wang, Shihua Zhao, Robert Chunhua Aging Dis Orginal Article Mesenchymal stem cells (MSCs) have beneficial effects on wound healing. MSCs function through direct cell-cell communication or indirectly through paracrine secretion of exosomes. Here, we found that MSC-derived exosomes had pro-wound healing effects via promotion of angiogenesis; however, this promoting effect was significantly reduced when senescence was induced in parental MSCs by hydrogen peroxide (H(2)O(2)). Further experiments showed that decreased miR-146a expression in exosomes derived from senescent MSCs (s-exo) contributed to these findings. In vitro, the pro-angiogenic effect of s-exo on tube formation in human umbilical vein endothelial cells was significantly reduced compared with that of exosomes derived from control MSCs (c-exo). In vivo, higher tube numbers and longer tube lengths were observed in the c-exo group compared with the s-exo group. Using microarray analysis, we found that miR-146a level in s-exo was lower than that in c-exo. Knockdown of miR-146a in c-exo decreased its capacity to promote angiogenesis, and overexpression of miR-146a in s-exo partially rescued its impaired pro-angiogenic capacity, thereby confirming that downregulation of miR-146a contributed to the reduced pro-wound healing capacity of s-exo. Our study is the first to demonstrate that cell senescence induced by H(2)O(2) alters the pro-angiogenic ability of exosomes by modulating the expression of exosomal miRNAs, especially miR-146a, thus providing new insights into the correlation between parental cell state and exosome content and function. JKL International LLC 2021-02-01 /pmc/articles/PMC7801275/ /pubmed/33532131 http://dx.doi.org/10.14336/AD.2020.0624 Text en copyright: © 2021 Xu et al. http://creativecommons.org/licenses/by/2.0/ this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Orginal Article
Xu, Meiqian
Su, Xiaodong
Xiao, Xian
Yu, Hongliang
Li, Xiaoxia
Keating, Armand
Wang, Shihua
Zhao, Robert Chunhua
Hydrogen Peroxide-Induced Senescence Reduces the Wound Healing-Promoting Effects of Mesenchymal Stem Cell-Derived Exosomes Partially via miR-146a
title Hydrogen Peroxide-Induced Senescence Reduces the Wound Healing-Promoting Effects of Mesenchymal Stem Cell-Derived Exosomes Partially via miR-146a
title_full Hydrogen Peroxide-Induced Senescence Reduces the Wound Healing-Promoting Effects of Mesenchymal Stem Cell-Derived Exosomes Partially via miR-146a
title_fullStr Hydrogen Peroxide-Induced Senescence Reduces the Wound Healing-Promoting Effects of Mesenchymal Stem Cell-Derived Exosomes Partially via miR-146a
title_full_unstemmed Hydrogen Peroxide-Induced Senescence Reduces the Wound Healing-Promoting Effects of Mesenchymal Stem Cell-Derived Exosomes Partially via miR-146a
title_short Hydrogen Peroxide-Induced Senescence Reduces the Wound Healing-Promoting Effects of Mesenchymal Stem Cell-Derived Exosomes Partially via miR-146a
title_sort hydrogen peroxide-induced senescence reduces the wound healing-promoting effects of mesenchymal stem cell-derived exosomes partially via mir-146a
topic Orginal Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801275/
https://www.ncbi.nlm.nih.gov/pubmed/33532131
http://dx.doi.org/10.14336/AD.2020.0624
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