Mesenchymal stem cells-derived extracellular vesicles-shuttled microRNA-223-3p suppress lipopolysaccharide-induced cardiac inflammation, pyroptosis, and dysfunction.
Int Immunopharmacol
; 110: 108910, 2022 Sep.
Article
em En
| MEDLINE
| ID: mdl-35978499
ABSTRACT
INTRODUCTION:
Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) possess therapeutical potentials in cardiac disorders. We probed into the mechanisms of MSC-EV-enclosed miR-223-3p in lipopolysaccharide (LPS)-induced cardiac inflammation, pyroptosis, and dysfunction.METHODS:
The cardiomyocyte model of cardiac dysfunction was induced by LPS, followed by determination of miR-223-3p expression. Next, we discerned the relation among miR-223-3p, FOXO3, and NLRP3. LPS-exposed cardiomyocytes were co-incubated with EVs from mouse MSCs to detect inflammation and pyroptosis using the gain- or loss-of-function experimentations. LPS-induced myocarditis mouse models were also prepared for further validating the effects of miR-223-3p from MSCs-derived EVs.RESULTS:
Reduced miR-223-3p was witnessed in LPS-induced cardiomyocytes. Specifically, miR-223-3p could target and inhibit FOXO3 to reduce NLRP3 expression. MSC-EVs could transfer miR-223-3p into cardiomyocytes to repress LPS-induced cardiomyocyte inflammation and pyroptosis. Additionally, in LPS-induced mice, pyroptosis, immune cell infiltration, inflammatory cytokine secretion, and cardiac dysfunction were alleviated by MSC-EV-loading miR-223-3p.CONCLUSION:
Conclusively, miR-223-3p shuttled by MSC-EVs restricted cardiac inflammation, pyroptosis, and dysfunction by disrupting FOXO3/NLRP3 axis.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Células-Tronco Mesenquimais
/
Vesículas Extracelulares
/
Cardiopatias
Limite:
Animals
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China