FTO-mediated RNA m 6 A methylation regulates synovial aggression and inflammation in rheumatoid arthritis

Fibroblast-like synoviocytes (FLS) plays an important role in synovial inflammation and joint damage in rheumatoid arthritis (RA). As the most abundant mRNA modification, N6-methyladenosine (m A) is involved in the development of various diseases; however, its role in RA remains to be defined. In th...

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Veröffentlicht in:Biochimica et biophysica acta. Molecular basis of disease 2024-10, Vol.1870 (7), p.167341
Hauptverfasser: Li, Ruiru, Kuang, Yu, Niu, Yuanyuan, Zhang, Shuoyang, Chen, Simin, Su, Fan, Wang, Jingnan, Lin, Shuibin, Liu, Di, Shen, Chuyu, Liang, Liuqin, Zheng, Song Guo, Jie, Ligang, Xiao, Youjun, Xu, Hanshi
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Sprache:eng
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Zusammenfassung:Fibroblast-like synoviocytes (FLS) plays an important role in synovial inflammation and joint damage in rheumatoid arthritis (RA). As the most abundant mRNA modification, N6-methyladenosine (m A) is involved in the development of various diseases; however, its role in RA remains to be defined. In this study, we reported the elevated expression of the m A demethylase fat mass and obesity-associated protein (FTO) in FLS and synovium from RA patients. Functionally, FTO knockdown or treatment with FB23-2, an inhibitor of the mRNA m A demethylase FTO, inhibited the migration, invasion and inflammatory response of RA FLS, however, FTO-overexpressed RA FLS exhibited increased migration, invasion and inflammatory response. We further demonstrated that FTO promoted ADAMTS15 mRNA stability in an m A-IGF2BP1 dependent manner. Notably, the severity of arthritis was significantly reduced in CIA mice with FB23-2 administration or CIA rats with intra-articular injection of FTO shRNA. Our results illustrate the contribution of FTO-mediated m A modification to joint damage and inflammation in RA and suggest that FTO might be a potential therapeutic target in RA.
ISSN:1879-260X