Genetic Deletion of FXR1 Reduces Intimal Hyperplasia and Induces Senescence in Vascular Smooth Muscle Cells.
Journal
The American journal of pathology
ISSN: 1525-2191
Titre abrégé: Am J Pathol
Pays: United States
ID NLM: 0370502
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
01
11
2022
revised:
21
12
2022
accepted:
12
01
2023
pmc-release:
01
05
2024
medline:
24
4
2023
pubmed:
21
4
2023
entrez:
20
04
2023
Statut:
ppublish
Résumé
Vascular smooth muscle cells (VSMC) play a critical role in the development and pathogenesis of intimal hyperplasia indicative of restenosis and other vascular diseases. Fragile-X related protein-1 (FXR1) is a muscle-enhanced RNA binding protein whose expression is increased in injured arteries. Previous studies suggest that FXR1 negatively regulates inflammation, but its causality in vascular disease is unknown. In the current study, RNA-sequencing of FXR1-depleted VSMC identified many transcripts with decreased abundance, most of which were associated with proliferation and cell division. mRNA abundance and stability of a number of these transcripts were decreased in FXR1-depleted hVSMC, as was proliferation (P < 0.05); however, increases in beta-galactosidase (P < 0.05) and γH2AX (P < 0.01), indicative of senescence, were noted. Further analysis showed increased abundance of senescence-associated genes with FXR1 depletion. A novel SMC-specific conditional knockout mouse (FXR1
Identifiants
pubmed: 37080662
pii: S0002-9440(23)00038-X
doi: 10.1016/j.ajpath.2023.01.006
pmc: PMC10155270
pii:
doi:
Substances chimiques
RNA, Messenger
0
Fxr1h protein, mouse
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
638-653Informations de copyright
Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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