FBN1 knockout promotes cervical artery dissection by inducing N-glycosylation alternation of extracellular matrix proteins in rat VSMCs.
Cell Signal
; 110: 110834, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37532137
ABSTRACT
FBN1 mutation promotes the degeneration of microfibril structures and extracellular matrix (ECM) integrity in the tunica media of the aorta in Marfan syndrome. However, whether FBN1 modulates cervical artery dissection (CAD) development and the potential molecular mechanisms of abnormal FBN1 in CAD remains elusive. In this study, FBN1 deficiency participated in the development of CAD and influenced the proliferation, apoptosis, and migration of vascular smooth muscle cells. FBN1 knockout induced alternations in mRNA levels of the transcriptome, protein expression of the proteome, and abundance of N-glycosylation of the N-glycoproteome. Comprehensive analysis of multiple omics showed up-regulation in mRNA levels of ECM proteins; yet, both the ECM protein levels and relative abundance of N-glycosylation were decreased. Moreover, we performed in vivo experiments to confirm the altered glycosylation of proteins in vascular smooth muscle cells. In conclusion, FBN1 deletion in vascular smooth muscle cells can result in altered N-glycosylation of ECM protein, which were critical for the stability of ECM and the process of CAD. This may open the way for a novel therapeutic strategy to treat people with CAD.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas da Matriz Extracelular
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Fibrilina-1
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Músculo Liso Vascular
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article