What is the clinical evidence from this study?

Study design: Other. Population: Rheumatoid arthritis. Intervention: GALNT1 knockdown vs. Control. Primary outcome: Migration, invasion, and arthritis severity.

What question did this study set out to answer?

This research aims to investigate how GALNT1-mediated O-glycosylation influences aggressive traits in rheumatoid synoviocytes and joint damage.

April 26, 2026JCI Insight0 citationsOpen Access

GALNT1 drives aggressive phenotypes of rheumatoid synoviocytes via NEK9 O‑glycosylation

YZYaoyao ZouChina Geological Survey HLHaobo LinChinese Academy of Sciences JSJianling SuGuangdong Academy of Medical Sciences

Key Result

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.

Key Points

This research aims to investigate how GALNT1-mediated O-glycosylation influences aggressive traits in rheumatoid synoviocytes and joint damage.
Targeted suppression of GALNT1 was performed in RA FLSs to assess migration and invasion.
A rat collagen-induced arthritis (CIA) model was used to evaluate arthritis severity.
In vitro experiments were conducted to analyze the effects of NEK9 O-glycosylation.
Suppression of GALNT1 significantly reduced migration and invasion in RA FLSs.
In the CIA model, arthritis severity was notably mitigated.
O-glycosylation of NEK9 by GALNT1 was shown to promote RA FLS pathogenicity by altering cytoskeleton structure and regulating ER stress.

Structured PICO

Does targeted suppression of GALNT1 reduce aggressive phenotypes of RA FLSs and arthritis severity in a rat CIA model?

Population

In vitro cultured human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) and healthy control (HC) FLSs; rat collagen-induced arthritis (CIA) model.

Intervention

Targeted suppression of GALNT1 (via siRNA in vitro, shGalnt1 adenovirus in vivo); NEK9 knockdown, overexpression, and site-directed mutagenesis.

Comparator

Healthy control FLSs, empty vector control, or wild-type NEK9.

Outcome

Migration and invasion of RA FLSs; arthritis severity in rat CIA model (paw edema, synovial inflammation, cartilage erosion).surrogate

GALNT1-mediated O-glycosylation of NEK9 promotes the pathogenic phenotype of RA FLSs, highlighting GALNT1 as a potential therapeutic target for rheumatoid arthritis.

Abstract

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.

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