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Autophagy regulates the effects of ADSC-derived small extracellular vesicles on acute lung injury
Small extracellular vesicles (sEVs) have been recognized to be more effective than direct stem cell differentiation into functional target cells in preventing tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lip...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185906/ https://www.ncbi.nlm.nih.gov/pubmed/35681240 http://dx.doi.org/10.1186/s12931-022-02073-y |
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author | Li, Chichi Wang, Min Wang, Wangjia Li, Yuping Zhang, Dan |
author_facet | Li, Chichi Wang, Min Wang, Wangjia Li, Yuping Zhang, Dan |
author_sort | Li, Chichi |
collection | PubMed |
description | Small extracellular vesicles (sEVs) have been recognized to be more effective than direct stem cell differentiation into functional target cells in preventing tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lipopolysaccharide (LPS)-induced acute lung injury and the effect of autophagy on ADSC functions, but the role of ADSC-derived sEVs (ADSC-sEVs) and autophagy-mediated regulation of ADSC-sEVs in LPS-induced pulmonary microvascular barrier damage remains unclear. After treatment with sEVs from ADSCs with or without autophagy inhibition, LPS-induced human pulmonary microvascular endothelial cell (HPMVECs) barrier damage was detected. LPS-induced acute lung injury in mice was assessed in vivo after intravenous administration of sEVs from ADSCs with or without autophagy inhibition. The effects of autophagy on the bioactive miRNA components of ADSC-sEVs were assessed after prior inhibition of cell autophagy. We found that ADSC-sEV effectively alleviated LPS-induced apoptosis, tight junction damage and high permeability of PMVECs. Moreover, in vivo administration of ADSC-sEV markedly inhibited LPS-triggered lung injury. However, autophagy inhibition, markedly weakened the therapeutic effect of ADSC-sEVs on LPS-induced PMVECs barrier damage and acute lung injury. In addition, autophagy inhibition, prohibited the expression of five specific miRNAs in ADSC-sEVs -under LPS-induced inflammatory conditions. Our results indicate that ADSC-sEVs protect against LPS-induced pulmonary microvascular barrier damage and acute lung injury. Autophagy is a positive mediator of sEVs function, at least in part through controlling the expression of bioactive miRNAs in sEVs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02073-y. |
format | Online Article Text |
id | pubmed-9185906 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91859062022-06-11 Autophagy regulates the effects of ADSC-derived small extracellular vesicles on acute lung injury Li, Chichi Wang, Min Wang, Wangjia Li, Yuping Zhang, Dan Respir Res Research Small extracellular vesicles (sEVs) have been recognized to be more effective than direct stem cell differentiation into functional target cells in preventing tissue injury and promoting tissue repair. Our previous study demonstrated the protective effect of adipose-derived stem cells (ADSCs) on lipopolysaccharide (LPS)-induced acute lung injury and the effect of autophagy on ADSC functions, but the role of ADSC-derived sEVs (ADSC-sEVs) and autophagy-mediated regulation of ADSC-sEVs in LPS-induced pulmonary microvascular barrier damage remains unclear. After treatment with sEVs from ADSCs with or without autophagy inhibition, LPS-induced human pulmonary microvascular endothelial cell (HPMVECs) barrier damage was detected. LPS-induced acute lung injury in mice was assessed in vivo after intravenous administration of sEVs from ADSCs with or without autophagy inhibition. The effects of autophagy on the bioactive miRNA components of ADSC-sEVs were assessed after prior inhibition of cell autophagy. We found that ADSC-sEV effectively alleviated LPS-induced apoptosis, tight junction damage and high permeability of PMVECs. Moreover, in vivo administration of ADSC-sEV markedly inhibited LPS-triggered lung injury. However, autophagy inhibition, markedly weakened the therapeutic effect of ADSC-sEVs on LPS-induced PMVECs barrier damage and acute lung injury. In addition, autophagy inhibition, prohibited the expression of five specific miRNAs in ADSC-sEVs -under LPS-induced inflammatory conditions. Our results indicate that ADSC-sEVs protect against LPS-induced pulmonary microvascular barrier damage and acute lung injury. Autophagy is a positive mediator of sEVs function, at least in part through controlling the expression of bioactive miRNAs in sEVs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12931-022-02073-y. BioMed Central 2022-06-09 2022 /pmc/articles/PMC9185906/ /pubmed/35681240 http://dx.doi.org/10.1186/s12931-022-02073-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Li, Chichi Wang, Min Wang, Wangjia Li, Yuping Zhang, Dan Autophagy regulates the effects of ADSC-derived small extracellular vesicles on acute lung injury |
title | Autophagy regulates the effects of ADSC-derived small extracellular vesicles on acute lung injury |
title_full | Autophagy regulates the effects of ADSC-derived small extracellular vesicles on acute lung injury |
title_fullStr | Autophagy regulates the effects of ADSC-derived small extracellular vesicles on acute lung injury |
title_full_unstemmed | Autophagy regulates the effects of ADSC-derived small extracellular vesicles on acute lung injury |
title_short | Autophagy regulates the effects of ADSC-derived small extracellular vesicles on acute lung injury |
title_sort | autophagy regulates the effects of adsc-derived small extracellular vesicles on acute lung injury |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9185906/ https://www.ncbi.nlm.nih.gov/pubmed/35681240 http://dx.doi.org/10.1186/s12931-022-02073-y |
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