Details

Autor(en) / Beteiligte

• Jia, Qian
• Che, Qincheng
• Zhang, Xiaoyu
• Chen, Jie
• Ren, Chunfeng
• Wu, Yunpeng
• Liang, Weiqiang
• Zhang, Xiaojie
• Li, Yanshan
• Li, Zunzhong
• Zhang, Zhenchun
• Shu, Qiang

Titel

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

Ist Teil von

• Biochemical pharmacology, 2024-02, Vol.220, p.115994-115994, Article 115994

Ort / Verlag

England

Erscheinungsjahr

2024

Link zum Volltext

Quelle

ScienceDirect

Beschreibungen/Notizen

• 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.