Exosomal Dvl3 promoted the aggressive phenotypic transformation of RA-FLS via wnt pathway.
Autoimmunity
; 55(5): 285-293, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35499309
ABSTRACT
OBJECTIVE:
This study was performed to explore the function and mechanism of Dvl3 in RA-FLS by exosome intervention.METHODS:
The expression pattern of Dvl3 was examined by IHC, WB, and qPCR. Modified exosomes obtained from culturing supernatant of RA-FLS infected with Dvl3 over expression (OE) lentivirus were administrated to the target RA-FLS. The ability of survival, migration, and the production of inflammatory factor influenced by exosomal Dvl3 were detected by CKK8 kits, Tunel, migration test, qPCR, and enzyme-linked immunosorbent assay (ELISA) respectively; Flow cytometry analysis was conducted to explorer the inflammatory moderate role of exosomes on CD4+ T cells. The possible downstream pathways of Dvl3 were screened by qPCR and WB and verified by double luciferase reporter experiment.RESULTS:
The expression level of Dvl3 was significantly increased in RA and CIA. Exosomes from the OE group could significantly promote cell proliferation activity, migration/invasion ability. The augment of TNF-α, IL-1ß, IL-17, and IL-21 was observed in exosomal Dvl3-OE group. Th1 and Th17 cells polarisation and cytokines related were both enhanced by Exosomal Dvl3. Over expression of Dvl3 was accompanied by the significant increase of ß-catenin and RhoA activities.CONCLUSION:
This study discovered the high expression of Dvl3 of exosomes derived from RA patients which may possessed the ability to promote phenotypic transformation of RA-FLS through Wnt pathway.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
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Membrana Sinovial
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Via de Sinalização Wnt
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Sinoviócitos
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Proteínas Desgrenhadas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article