Knockdown of Galectin-9 alleviates rheumatoid arthritis through suppressing TNF--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 fibroblastlike 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-alpha) inhibitor treatment in the plasma of patients with RA. Additionally, transcriptome sequencing revealed that Gal -9 was involved in the regulation of the TNF-alpha pathway. Gal -9 was considerably upregulated after TNF-alpha stimulation in FLSs, and knockdown of Gal9 substantially inhibited TNF-alpha 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-alpha induced activation in RA through MAFB, PI3K/AKT/mTOR.