Suppression of smooth muscle cell inflammation by myocardin-related transcription factors involves inactivation of TANK-binding kinase 1.
Sci Rep
; 14(1): 13321, 2024 06 10.
Article
em En
| MEDLINE
| ID: mdl-38858497
ABSTRACT
Myocardin-related transcription factors (MRTFs myocardin/MYOCD, MRTF-A/MRTFA, and MRTF-B/MRTFB) suppress production of pro-inflammatory cytokines and chemokines in human smooth muscle cells (SMCs) through sequestration of RelA in the NF-κB complex, but additional mechanisms are likely involved. The cGAS-STING pathway is activated by double-stranded DNA in the cytosolic compartment and acts through TANK-binding kinase 1 (TBK1) to spark inflammation. The present study tested if MRTFs suppress inflammation also by targeting cGAS-STING signaling. Interrogation of a transcriptomic dataset where myocardin was overexpressed using a panel of 56 cGAS-STING cytokines showed the panel to be repressed. Moreover, MYOCD, MRTFA, and SRF associated negatively with the panel in human arteries. RT-qPCR in human bronchial SMCs showed that all MRTFs reduced pro-inflammatory cytokines on the panel. MRTFs diminished phosphorylation of TBK1, while STING phosphorylation was marginally affected. The TBK1 inhibitor amlexanox, but not the STING inhibitor H-151, reduced the anti-inflammatory effect of MRTF-A. Co-immunoprecipitation and proximity ligation assays supported binding between MRTF-A and TBK1 in SMCs. MRTFs thus appear to suppress cellular inflammation in part by acting on the kinase TBK1. This may defend SMCs against pro-inflammatory insults in disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Transativadores
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Proteínas Serina-Treonina Quinases
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Miócitos de Músculo Liso
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Inflamação
Limite:
Humans
Idioma:
En
Revista:
Sci Rep
/
Sci. rep. (Nat. Publ. Group)
/
Scientific reports (Nature Publishing Group)
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suécia