Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Inhibit Apoptosis of Pulmonary Microvascular Endothelial Cells in COPD Mice Through miR-30b/Wnt5a Pathway

Qing Song,1– 4 Aiyuan Zhou,5 Wei Cheng,1– 4 Yiyang Zhao,6 Cong Liu,1– 4 Yuqin Zeng,1– 4 Ling Lin,1– 4 Zijing Zhou,1– 4 Yating Peng,1– 4 Ping Chen1– 4 1Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republ...

Full description

Saved in:
Bibliographic Details
Main Authors: Song Q, Zhou A, Cheng W, Zhao Y, Liu C, Zeng Y, Lin L, Zhou Z, Peng Y, Chen P
Format: Article
Language:English
Published: Dove Medical Press 2025-01-01
Series:International Journal of Nanomedicine
Subjects:
Online Access:https://www.dovepress.com/bone-marrow-mesenchymal-stem-cells-derived-exosomes-inhibit-apoptosis--peer-reviewed-fulltext-article-IJN
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832577711645655040
author Song Q
Zhou A
Cheng W
Zhao Y
Liu C
Zeng Y
Lin L
Zhou Z
Peng Y
Chen P
author_facet Song Q
Zhou A
Cheng W
Zhao Y
Liu C
Zeng Y
Lin L
Zhou Z
Peng Y
Chen P
author_sort Song Q
collection DOAJ
description Qing Song,1– 4 Aiyuan Zhou,5 Wei Cheng,1– 4 Yiyang Zhao,6 Cong Liu,1– 4 Yuqin Zeng,1– 4 Ling Lin,1– 4 Zijing Zhou,1– 4 Yating Peng,1– 4 Ping Chen1– 4 1Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, 410011, People’s Republic of China; 3Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 4Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, the Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China; 6Ultrasound Imaging Department, Xiangya Hospital of Central South University, Changsha, Hunan, 410083, People’s Republic of ChinaCorrespondence: Ping Chen, Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Renmin Middle Road, Changsha, Hunan, 410011, People’s Republic of China, Tel 13873115563, Email pingchen0731@csu.edu.cnBackground: Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes are rich in a variety of active substances, including microRNA (miR) and have shown powerful therapeutic effects to ameliorate cell injury and diseases. However, the role of BMSCs-derived exosomes on chronic obstructive pulmonary disease (COPD) has been poorly studied. In addition, pulmonary microvascular endothelial cells (PMVECs) apoptosis contributes to the onset of COPD. Inhibition of PMVECs apoptosis can reverse COPD changes. Therefore, the aim of this study was to explore the role of BMSCs-derived exosomes in the apoptosis of PMVECs in COPD and to investigate the potential mechanisms.Methods: We isolated and characterized normal mouse BMSCs-derived exosomes and PMVECs. We performed miR sequencing of BMSCs-derived exosomes. We transfected PMVECs with the miR-30b mimic and Wnt5a overexpression plasmid to assess the underlying mechanisms. Cigarette smoke extract (CSE)-induced COPD mice were treated with exosomes and HBLV-mmu-miR-30b via intratracheal instillation. Finally, we determined the expression of miR-30b and Wnt5a in tissues from patients with COPD.Results: BMSCs-derived exosomes could significantly reduce apoptosis of CSE-induced PMVECs and increase the expression of miR-30b (p< 0.05). Based on miR sequencing, miR-30b was highly enriched in BMSCs-derived exosomes. The knockdown of miR-30b in BMSCs-derived exosomes could increase the apoptosis of CSE-induced PMVECs (p< 0.05). miR-30b overexpression significantly reduced apoptosis and repressed Wnt5a protein expression in CSE-induced PMVECs (p< 0.05). Furthermore, Wnt5a overexpression reversed the anti-apoptotic effect of miR-30b on CSE-induced PMVECs (p< 0.05). In addition, compared with the COPD group, treatment with BMSCs-derived exosomes and miR-30b overexpression could alleviate emphysema changes, decrease the mean linear intercept and alveolar destructive index, reduce apoptosis, increase the expression of miR-30b, and decrease the expression of Wnt5a in lung tissue (p< 0.05). Finally, miR-30b expression was decreased in patients with COPD, while Wnt5a expression was increased in these patients (p< 0.05).Conclusion: BMSCs-derived exosomes could improve the damage of COPD perhaps by delivering miR-30b. miR-30b could reduce apoptosis of CSE-induced PMVECs by targeting Wnt5a. Keywords: chronic obstructive pulmonary disease, bone marrow mesenchymal stem cells, exosomes, miR-30b, Wnt5a
format Article
id doaj-art-f837d2f6189f4b91a3aeb21b4a854be1
institution Kabale University
issn 1178-2013
language English
publishDate 2025-01-01
publisher Dove Medical Press
record_format Article
series International Journal of Nanomedicine
spelling doaj-art-f837d2f6189f4b91a3aeb21b4a854be12025-01-30T18:07:17ZengDove Medical PressInternational Journal of Nanomedicine1178-20132025-01-01Volume 201191121199722Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Inhibit Apoptosis of Pulmonary Microvascular Endothelial Cells in COPD Mice Through miR-30b/Wnt5a PathwaySong QZhou ACheng WZhao YLiu CZeng YLin LZhou ZPeng YChen PQing Song,1– 4 Aiyuan Zhou,5 Wei Cheng,1– 4 Yiyang Zhao,6 Cong Liu,1– 4 Yuqin Zeng,1– 4 Ling Lin,1– 4 Zijing Zhou,1– 4 Yating Peng,1– 4 Ping Chen1– 4 1Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, 410011, People’s Republic of China; 3Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 4Research Unit of Respiratory Disease, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, the Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People’s Republic of China; 6Ultrasound Imaging Department, Xiangya Hospital of Central South University, Changsha, Hunan, 410083, People’s Republic of ChinaCorrespondence: Ping Chen, Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Renmin Middle Road, Changsha, Hunan, 410011, People’s Republic of China, Tel 13873115563, Email pingchen0731@csu.edu.cnBackground: Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes are rich in a variety of active substances, including microRNA (miR) and have shown powerful therapeutic effects to ameliorate cell injury and diseases. However, the role of BMSCs-derived exosomes on chronic obstructive pulmonary disease (COPD) has been poorly studied. In addition, pulmonary microvascular endothelial cells (PMVECs) apoptosis contributes to the onset of COPD. Inhibition of PMVECs apoptosis can reverse COPD changes. Therefore, the aim of this study was to explore the role of BMSCs-derived exosomes in the apoptosis of PMVECs in COPD and to investigate the potential mechanisms.Methods: We isolated and characterized normal mouse BMSCs-derived exosomes and PMVECs. We performed miR sequencing of BMSCs-derived exosomes. We transfected PMVECs with the miR-30b mimic and Wnt5a overexpression plasmid to assess the underlying mechanisms. Cigarette smoke extract (CSE)-induced COPD mice were treated with exosomes and HBLV-mmu-miR-30b via intratracheal instillation. Finally, we determined the expression of miR-30b and Wnt5a in tissues from patients with COPD.Results: BMSCs-derived exosomes could significantly reduce apoptosis of CSE-induced PMVECs and increase the expression of miR-30b (p< 0.05). Based on miR sequencing, miR-30b was highly enriched in BMSCs-derived exosomes. The knockdown of miR-30b in BMSCs-derived exosomes could increase the apoptosis of CSE-induced PMVECs (p< 0.05). miR-30b overexpression significantly reduced apoptosis and repressed Wnt5a protein expression in CSE-induced PMVECs (p< 0.05). Furthermore, Wnt5a overexpression reversed the anti-apoptotic effect of miR-30b on CSE-induced PMVECs (p< 0.05). In addition, compared with the COPD group, treatment with BMSCs-derived exosomes and miR-30b overexpression could alleviate emphysema changes, decrease the mean linear intercept and alveolar destructive index, reduce apoptosis, increase the expression of miR-30b, and decrease the expression of Wnt5a in lung tissue (p< 0.05). Finally, miR-30b expression was decreased in patients with COPD, while Wnt5a expression was increased in these patients (p< 0.05).Conclusion: BMSCs-derived exosomes could improve the damage of COPD perhaps by delivering miR-30b. miR-30b could reduce apoptosis of CSE-induced PMVECs by targeting Wnt5a. Keywords: chronic obstructive pulmonary disease, bone marrow mesenchymal stem cells, exosomes, miR-30b, Wnt5ahttps://www.dovepress.com/bone-marrow-mesenchymal-stem-cells-derived-exosomes-inhibit-apoptosis--peer-reviewed-fulltext-article-IJNchronic obstructive pulmonary diseasebone marrow mesenchymal stem cellsexosomesmir-30bwnt5a
spellingShingle Song Q
Zhou A
Cheng W
Zhao Y
Liu C
Zeng Y
Lin L
Zhou Z
Peng Y
Chen P
Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Inhibit Apoptosis of Pulmonary Microvascular Endothelial Cells in COPD Mice Through miR-30b/Wnt5a Pathway
International Journal of Nanomedicine
chronic obstructive pulmonary disease
bone marrow mesenchymal stem cells
exosomes
mir-30b
wnt5a
title Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Inhibit Apoptosis of Pulmonary Microvascular Endothelial Cells in COPD Mice Through miR-30b/Wnt5a Pathway
title_full Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Inhibit Apoptosis of Pulmonary Microvascular Endothelial Cells in COPD Mice Through miR-30b/Wnt5a Pathway
title_fullStr Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Inhibit Apoptosis of Pulmonary Microvascular Endothelial Cells in COPD Mice Through miR-30b/Wnt5a Pathway
title_full_unstemmed Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Inhibit Apoptosis of Pulmonary Microvascular Endothelial Cells in COPD Mice Through miR-30b/Wnt5a Pathway
title_short Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Inhibit Apoptosis of Pulmonary Microvascular Endothelial Cells in COPD Mice Through miR-30b/Wnt5a Pathway
title_sort bone marrow mesenchymal stem cells derived exosomes inhibit apoptosis of pulmonary microvascular endothelial cells in copd mice through mir 30b wnt5a pathway
topic chronic obstructive pulmonary disease
bone marrow mesenchymal stem cells
exosomes
mir-30b
wnt5a
url https://www.dovepress.com/bone-marrow-mesenchymal-stem-cells-derived-exosomes-inhibit-apoptosis--peer-reviewed-fulltext-article-IJN
work_keys_str_mv AT songq bonemarrowmesenchymalstemcellsderivedexosomesinhibitapoptosisofpulmonarymicrovascularendothelialcellsincopdmicethroughmir30bwnt5apathway
AT zhoua bonemarrowmesenchymalstemcellsderivedexosomesinhibitapoptosisofpulmonarymicrovascularendothelialcellsincopdmicethroughmir30bwnt5apathway
AT chengw bonemarrowmesenchymalstemcellsderivedexosomesinhibitapoptosisofpulmonarymicrovascularendothelialcellsincopdmicethroughmir30bwnt5apathway
AT zhaoy bonemarrowmesenchymalstemcellsderivedexosomesinhibitapoptosisofpulmonarymicrovascularendothelialcellsincopdmicethroughmir30bwnt5apathway
AT liuc bonemarrowmesenchymalstemcellsderivedexosomesinhibitapoptosisofpulmonarymicrovascularendothelialcellsincopdmicethroughmir30bwnt5apathway
AT zengy bonemarrowmesenchymalstemcellsderivedexosomesinhibitapoptosisofpulmonarymicrovascularendothelialcellsincopdmicethroughmir30bwnt5apathway
AT linl bonemarrowmesenchymalstemcellsderivedexosomesinhibitapoptosisofpulmonarymicrovascularendothelialcellsincopdmicethroughmir30bwnt5apathway
AT zhouz bonemarrowmesenchymalstemcellsderivedexosomesinhibitapoptosisofpulmonarymicrovascularendothelialcellsincopdmicethroughmir30bwnt5apathway
AT pengy bonemarrowmesenchymalstemcellsderivedexosomesinhibitapoptosisofpulmonarymicrovascularendothelialcellsincopdmicethroughmir30bwnt5apathway
AT chenp bonemarrowmesenchymalstemcellsderivedexosomesinhibitapoptosisofpulmonarymicrovascularendothelialcellsincopdmicethroughmir30bwnt5apathway