Mesenchymal stem cells-derived exosomal miRNA-28-3p promotes apoptosis of pulmonary endothelial cells in pulmonary embolism
H.-Y. Mao, L.-N. Liu, Y.-M. Hu Department of Cardiovascular Medicine, Cangzhou Central Hospital, Cangzhou, Hebei, China. huyamin091@163.com
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.
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To cite this article
H.-Y. Mao, L.-N. Liu, Y.-M. Hu
Mesenchymal stem cells-derived exosomal miRNA-28-3p promotes apoptosis of pulmonary endothelial cells in pulmonary embolism
Eur Rev Med Pharmacol Sci
Year: 2020
Vol. 24 - N. 20
Pages: 10619-10631
DOI: 10.26355/eurrev_202010_23420