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FTO-mediated RNA m6A methylation regulates synovial aggression and inflammation in rheumatoid arthritis.
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.
Afiliación
  • Li R; Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Kuang Y; Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Niu Y; Department of General Practice, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Zhang S; Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Chen S; Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Su F; Department of Geriatrics, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Wang J; Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Lin S; Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Liu D; Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Shen C; Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Liang L; Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
  • Zheng SG; Department of Immunology, School of Cell and Gene Therapy, Song Jiang Research Institutes, Shanghai Jiaotong University, School of Medicine, Shanghai, China.
  • Jie L; Department of Rheumatology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address: jieligang1976@smu.edu.cn.
  • Xiao Y; Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China. Electronic address: xiaoyouj@mail2.sysu.edu.cn.
  • Xu H; Department of Rheumatology and Immunology, the First Affiliated Hospital, Sun Yat-sen University, No.58 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China. Electronic address: xuhanshi@mail.sysu.edu.cn.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167341, 2024 10.
Article en En | MEDLINE | ID: mdl-39025373
ABSTRACT
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 (m6A) 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 m6A 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 m6A 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 m6A-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 m6A modification to joint damage and inflammation in RA and suggest that FTO might be a potential therapeutic target in RA.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Adenosina / Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato / Metilación de ARN / Inflamación Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artritis Reumatoide / Adenosina / Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato / Metilación de ARN / Inflamación Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos