Targeted suppression of GALNT1 curtailed migration and invasion in rheumatoid arthritis fibroblast-like synoviocytes and mitigated arthritis severity in a rat collagen-induced arthritis model.
Does targeted suppression of GALNT1 reduce aggressive phenotypes of RA FLSs and arthritis severity in a rat CIA model?
GALNT1-mediated O-glycosylation of NEK9 promotes the pathogenic phenotype of RA FLSs, highlighting GALNT1 as a potential therapeutic target for rheumatoid arthritis.
Fibroblast-like synoviocytes (FLSs) are crucial in driving synovial inflammation and joint damage in rheumatoid arthritis (RA). This study explored the functions and underlying mechanisms of GALNT1-mediated O-glycosylation, which is markedly upregulated in RA FLSs, in synovial aggression and subsequent experimental joint damage. Targeted suppression of GALNT1 effectively curtailed migration and invasion in RA FLSs and mitigated arthritis severity in a rat collagen-induced arthritis (CIA) model. Mechanistically, NEK9 was identified as a pivotal substrate and downstream effector of GALNT1, affecting the aggressive phenotype of RA FLSs. In vitro experiments further demonstrated that O-glycosylation of NEK9, mediated by GALNT1, promotes the pathogenic phenotype of RA FLSs by promoting cytoskeleton reorganization and restraining excessive endoplasmic reticulum (ER) stress activation. Our study provides mechanistic insights into the activation of RA FLSs and identifies GALNT1 as a potential therapeutic target for RA.
Zou et al. (Thu,) conducted a other in Rheumatoid arthritis. GALNT1 knockdown vs. Control was evaluated on Migration, invasion, and arthritis severity. Targeted suppression of GALNT1 curtailed migration and invasion in rheumatoid arthritis fibroblast-like synoviocytes and mitigated arthritis severity in a rat collagen-induced arthritis model.