Mesenchymal stem cells-derived exosomal miRNA-28-3p promotes apoptosis of pulmonary endothelial cells in pulmonary embolism.
Eur Rev Med Pharmacol Sci
; 24(20): 10619-10631, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-33155220
ABSTRACT
OBJECTIVE:
Pulmonary embolism (PE) is a primary clinical manifestation of venous thromboembolism (VTE). It has been demonstrated that pulmonary endothelial cells (PECs) are apoptotic-resistant in PE. MATERIALS ANDMETHODS:
In this study, PECs were collected from PE patients and mouse models. Western blot, RT-PCR, flow cytometry, H&E and TUNEL assay, confocal and TEM microscopy, and Luciferase reporter assay were performed to determine the effects of miR-28-3p on PECs apoptosis and if exosomes can act as the shuttle to transport miR-28-3p to PECs.RESULTS:
The results revealed that apoptosis and miR-28-3p were downregulated in PECs of PE. The miR-28-3p mimics and inhibitor enhanced and further inhibited apoptosis in PECs, respectively. Both miR-28-3p-modified adipose tissue-derived mesenchymal stem cells (AMSCs) and AMSC-derived exosomes upregulated miR-28-3p expression in PECs, leading to elevated apoptosis of PECs. Apoptosis inhibitor 5 (API5) was a direct target gene of miR-28-3p, and the overexpression of API5 in miR-28-3p-modified PECs further suppressed apoptosis. Furthermore, the administration of miR-28-3p-modified exosomes to PE mouse model promoted apoptosis in PECs.CONCLUSIONS:
Exosomal miR-28-3p could ameliorate PE-associated apoptosis-resistance in PECs through targeting API5 in vitro and in vivo. Therefore, AMSCs-derived exosome is a promising way to deliver functioning miRNA to PECs, providing insight into novel therapy of PE.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Embolia Pulmonar
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Apoptose
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MicroRNAs
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Células Endoteliais
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Exossomos
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Células-Tronco Mesenquimais
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article