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microRNA‐106b derived from endothelial cell–secreted extracellular vesicles prevents skin wound healing by inhibiting JMJD3 and RIPK3

Intriguingly, microRNAs (miRs) transferred as cargo in extracellular vesicles (EVs) can modulate wound healing through their regulation of fibroblast functions. In this study, we investigated the effects of miR‐106b transfer via EVs derived from human umbilical vein endothelial cells (HUVECs) on ski...

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Detalles Bibliográficos
Autores principales: Qi, Lin, Lu, Yufeng, Wang, Zhaolin, Zhang, Guiyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107101/
https://www.ncbi.nlm.nih.gov/pubmed/33734576
http://dx.doi.org/10.1111/jcmm.16037
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author Qi, Lin
Lu, Yufeng
Wang, Zhaolin
Zhang, Guiyun
author_facet Qi, Lin
Lu, Yufeng
Wang, Zhaolin
Zhang, Guiyun
author_sort Qi, Lin
collection PubMed
description Intriguingly, microRNAs (miRs) transferred as cargo in extracellular vesicles (EVs) can modulate wound healing through their regulation of fibroblast functions. In this study, we investigated the effects of miR‐106b transfer via EVs derived from human umbilical vein endothelial cells (HUVECs) on skin wound healing. Dual‐luciferase reporter gene assay identified that miR‐106b could target and inhibit JMJD3. RT‐qPCR analysis showed EVs isolated from HUVECs had enriched expression of miR‐106b. LL29 fibroblast cells and HaCaT keratinocytes were co‐cultured with HUVEC‐derived EVs, in which miR‐106b had been up‐regulated or down‐regulated by its mimic or inhibitor. The co‐culture with HUVEC‐derived EVs increased miR‐106b expression, and reduced the viability and adhesion of LL29 and HaCaT cells, whereas the inhibition of miR‐106b in HUVEC‐derived EVs enhanced the viability and adhesion of LL29 and HaCaT cells through up‐regulation of JMJD3. Next, we showed that JMJD3 overexpression enhanced LL29 and HaCaT cell viability and adhesion through elevating RIPK3, which induced the phosphorylation of AKT during the wound‐healing process. We next developed a mouse skin wound model to investigate the actions of miR‐106b in vivo after 14 days. The delivery of miR‐106b via HUVEC‐derived EVs delayed wound healing through suppression of collagen I content and angiogenesis, but had no effects on pro‐inflammatory cytokines. In conclusion, miR‐106b from HUVEC‐derived EVs inhibits JMJD3 and RIPK3, leading to the inhibition of skin wound healing, thus constituting a new therapeutic target.
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spelling pubmed-81071012021-05-10 microRNA‐106b derived from endothelial cell–secreted extracellular vesicles prevents skin wound healing by inhibiting JMJD3 and RIPK3 Qi, Lin Lu, Yufeng Wang, Zhaolin Zhang, Guiyun J Cell Mol Med Original Articles Intriguingly, microRNAs (miRs) transferred as cargo in extracellular vesicles (EVs) can modulate wound healing through their regulation of fibroblast functions. In this study, we investigated the effects of miR‐106b transfer via EVs derived from human umbilical vein endothelial cells (HUVECs) on skin wound healing. Dual‐luciferase reporter gene assay identified that miR‐106b could target and inhibit JMJD3. RT‐qPCR analysis showed EVs isolated from HUVECs had enriched expression of miR‐106b. LL29 fibroblast cells and HaCaT keratinocytes were co‐cultured with HUVEC‐derived EVs, in which miR‐106b had been up‐regulated or down‐regulated by its mimic or inhibitor. The co‐culture with HUVEC‐derived EVs increased miR‐106b expression, and reduced the viability and adhesion of LL29 and HaCaT cells, whereas the inhibition of miR‐106b in HUVEC‐derived EVs enhanced the viability and adhesion of LL29 and HaCaT cells through up‐regulation of JMJD3. Next, we showed that JMJD3 overexpression enhanced LL29 and HaCaT cell viability and adhesion through elevating RIPK3, which induced the phosphorylation of AKT during the wound‐healing process. We next developed a mouse skin wound model to investigate the actions of miR‐106b in vivo after 14 days. The delivery of miR‐106b via HUVEC‐derived EVs delayed wound healing through suppression of collagen I content and angiogenesis, but had no effects on pro‐inflammatory cytokines. In conclusion, miR‐106b from HUVEC‐derived EVs inhibits JMJD3 and RIPK3, leading to the inhibition of skin wound healing, thus constituting a new therapeutic target. John Wiley and Sons Inc. 2021-03-18 2021-05 /pmc/articles/PMC8107101/ /pubmed/33734576 http://dx.doi.org/10.1111/jcmm.16037 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Qi, Lin
Lu, Yufeng
Wang, Zhaolin
Zhang, Guiyun
microRNA‐106b derived from endothelial cell–secreted extracellular vesicles prevents skin wound healing by inhibiting JMJD3 and RIPK3
title microRNA‐106b derived from endothelial cell–secreted extracellular vesicles prevents skin wound healing by inhibiting JMJD3 and RIPK3
title_full microRNA‐106b derived from endothelial cell–secreted extracellular vesicles prevents skin wound healing by inhibiting JMJD3 and RIPK3
title_fullStr microRNA‐106b derived from endothelial cell–secreted extracellular vesicles prevents skin wound healing by inhibiting JMJD3 and RIPK3
title_full_unstemmed microRNA‐106b derived from endothelial cell–secreted extracellular vesicles prevents skin wound healing by inhibiting JMJD3 and RIPK3
title_short microRNA‐106b derived from endothelial cell–secreted extracellular vesicles prevents skin wound healing by inhibiting JMJD3 and RIPK3
title_sort microrna‐106b derived from endothelial cell–secreted extracellular vesicles prevents skin wound healing by inhibiting jmjd3 and ripk3
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107101/
https://www.ncbi.nlm.nih.gov/pubmed/33734576
http://dx.doi.org/10.1111/jcmm.16037
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