4.8 Article

Epigenetic regulator UHRF1 orchestrates proinflammatory gene expression in rheumatoid arthritis in a suppressive manner

期刊

JOURNAL OF CLINICAL INVESTIGATION
卷 132, 期 11, 页码 -

出版社

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI150533

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资金

  1. Japan Society for the Promotion of Science (JSPS) KAKENHI [JP17K17929, JP19K16015, JP23689066, JP15H04961, JP15K15552, JP17K19728, JP19H03786]
  2. Osaka Medical Research Foundation for Intractable Diseases
  3. Takeda Science Foundation Medical Research grant
  4. UCB Japan (UCBJ)
  5. Japanese Society for Bone and Mineral Research (JSBMR), Frontier Scientist grant 2019

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The study reveals that UHRF1 is a central epigenetic regulator in rheumatoid arthritis (RA) pathogenesis, playing a suppressive role in multiple disease processes. Stabilizing UHRF1 through Ryuvidine administration ameliorates the pathogenic events in arthritis, suggesting that targeting UHRF1 could be a therapeutic strategy for RA.
Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation with aberrant epigenetic alterations, eventually leading to joint destruction. However, the epigenetic regulatory mechanisms underlying RA pathogenesis remain largely unknown. Here, we showed that ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) is a central epigenetic regulator that orchestrates multiple pathogeneses in RA in a suppressive manner. UHRF1 expression was remarkably Finally, Ryuvidine administration stabilized UHRF1 ameliorated arthritis pathogeneses in a mouse model of RA. This study pathogenic events in arthritis, suggesting that targeting UHRF1 could be one of the therapeutic strategies for RA.

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