DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis.
Nat Commun
; 8: 14252, 2017 02 06.
Article
en En
| MEDLINE
| ID: mdl-28165452
ABSTRACT
Novel therapeutics are required for improving the management of chronic inflammatory diseases. Aptamers are single-stranded RNA or DNA molecules that have recently shown utility in a clinical setting, as they can specifically neutralize biomedically relevant proteins, particularly cell surface and extracellular proteins. The nuclear chromatin protein DEK is a secreted chemoattractant that is abundant in the synovia of patients with juvenile idiopathic arthritis (JIA). Here, we show that DEK is crucial to the development of arthritis in mouse models, thus making it an appropriate target for aptamer-based therapy. Genetic depletion of DEK or treatment with DEK-targeted aptamers significantly reduces joint inflammation in vivo and greatly impairs the ability of neutrophils to form neutrophil extracellular traps (NETs). DEK is detected in spontaneously forming NETs from JIA patient synovial neutrophils, and DEK-targeted aptamers reduce NET formation. DEK is thus key to joint inflammation, and anti-DEK aptamers hold promise for the treatment of JIA and other types of arthritis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis Juvenil
/
Proteínas Cromosómicas no Histona
/
Factores Quimiotácticos
/
Proteínas Oncogénicas
/
Proteínas de Unión al ADN
/
Aptámeros de Nucleótidos
/
Trampas Extracelulares
/
Proteínas de Unión a Poli-ADP-Ribosa
Tipo de estudio:
Prognostic_studies
Límite:
Adult
/
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos