M2 macrophagederived exosomes alleviate KCa3.1 channel expression in rapidly paced HL1 myocytes via the NFκB (p65)/STAT3 signaling pathway.
Mol Med Rep
; 29(4)2024 04.
Article
em En
| MEDLINE
| ID: mdl-38334149
ABSTRACT
The present study was designed to explore the role of M2 macrophagederived exosomes (M2exos) on the KCa3.1 channel in a cellular atrial fibrillation (AF) model using rapidly paced HL1 myocytes. M2 macrophages and M2exos were isolated and identified. MicroRNA (miR)146a5p levels in M2 macrophages and M2exos were quantified using reverse transcriptionquantitative PCR (RTqPCR). HL1 myocytes were randomly divided into six groups Control group, pacing group, pacing + coculture group (pacing HL1 cells cocultured with M2exos), pacing + mimicmiR146a5p group, pacing + NCmiR146a5p group and pacing + pyrrolidine dithiocarbamate (PDTC; a special blocker of the NFκB signaling pathway) group. Transmission electron microscopy, nanoparticle tracking analysis, western blotting, RTqPCR and immunohistochemistry were performed in the present study. A wholecell clamp was also applied to record the current density of KCa3.1 and action potential duration (APD) in each group. The results revealed that miR146a5p was highly expressed in both M2 macrophages and M2exos. Pacing HL1 cells led to a shorter APD, an increased KCa3.1 current density and higher protein levels of KCa3.1, phosphorylated (p)NFκB p65, pSTAT3 and IL1ß compared with the control group. M2exos, miR146a5pmimic and PDTC both reduced the protein expression of KCa3.1, pNFκB p65, pSTAT3 and IL1ß and the current density of KCa3.1, resulting in a longer APD in the pacing HL1 cells. In conclusion, M2exos and their cargo, which comprised miR146a5p, decreased KCa3.1 expression and IL1ß secretion in pacing HL1 cells via the NFκB/STAT3 signaling pathway, limiting the shorter APD caused by rapid pacing.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Fibrilação Atrial
/
Tiocarbamatos
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Prolina
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MicroRNAs
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Exossomos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2024
Tipo de documento:
Article