Knockdown of Galectin-9 alleviates rheumatoid arthritis through suppressing TNF-α-induced activation of fibroblast-like synoviocytes.

The role of Galectin-9 (Gal-9) in the pathogenesis of rheumatoid arthritis (RA) remains unclear. This study aimed to investigate the mechanism of action and therapeutic potential of Gal-9 in RA. We detected Gal-9 expression in clinical samples, explored the mechanism of function of Gal-9 by knockdown and overexpression in fibroblast-like synoviocytes (FLSs), and further verified it in collagen-induced arthritis (CIA) model. We found that the levels of Gal-9 were considerably elevated in RA synovium than in osteoarthritis (OA) patients. A substantial decrease of Gal-9 was demonstrated after tumor necrosis factor (TNF-α) inhibitor treatment in the plasma of patients with RA. Additionally, transcriptome sequencing revealed that Gal-9 was involved in the regulation of the TNF-α pathway. Gal-9 was considerably upregulated after TNF-α stimulation in FLSs, and knockdown of Gal-9 substantially inhibited TNF-α activated proliferation, migration and inflammatory response. According to cell transcriptome sequencing results, we further confirmed that Gal-9 could achieve these effects by interacting with MAFB and affecting PI3K/AKT/mTOR pathway. Finally, we knocked down Gal-9 on the CIA model and found that it could alleviate the progression of arthritis. In conclusion, our study revealed that the knockdown of Gal-9 could inhibited TNF-α induced activation in RA through MAFB, PI3K/AKT/mTOR.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)