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Mesenchymal stem cells-derived exosomal miRNA-28-3p promotes apoptosis of pulmonary endothelial cells in pulmonary embolism.

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 AND METHODS: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.

journal_name

Eur Rev Med Pharmacol Sci

journal_title

European review for medical and pharmacological sciences

authors

Mao HY,Liu LN,Hu YM

doi

10.26355/eurrev_202010_23420

subject

Has Abstract

pub_date

2020-10-01 00:00:00

pages

10619-10631

issue

20

eissn

1128-3602

issn

2284-0729

journal_volume

24

pub_type

杂志文章

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