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

被引:14
|
作者
Saeki, Noritaka [1 ,2 ]
Inoue, Kazuki [3 ]
Ideta-Otsuka, Maky [4 ]
Watamori, Kunihiko [5 ]
Mizuki, Shinichi [6 ]
Takenaka, Katsuto [7 ]
Igarashi, Katsuhide [8 ,9 ]
Miura, Hiromasa [5 ]
Takeda, Shu [10 ]
Imai, Yuuki [1 ,2 ,11 ]
机构
[1] Ehime Univ, Adv Res Support Ctr, Div Lab Anim Res, Toon, Ehime, Japan
[2] Ehime Univ, Proteosci Ctr, Div Integrat Pathophysiol, Toon, Ehime, Japan
[3] Nankai Univ, Nankai Int Adv Res Inst Shenzhen Futian, Shenzhen, Peoples R China
[4] Hoshi Univ, Sch Pharm & Pharmaceut Sci, Lab Instrumental Anal, Shinagawa Ku, Tokyo, Japan
[5] Ehime Univ, Grad Sch Med, Dept Bone & Joint Surg, Toon, Ehime, Japan
[6] Matsuyama Red Cross Hosp, Ctr Rheumat Dis, Matsuyama, Ehime, Japan
[7] Ehime Univ, Grad Sch Med, Dept Hematol Clin Immunol & Infect Dis, Toon, Ehime, Japan
[8] Hoshi Univ, Sch Pharm & Pharmaceut Sci, Lab Biofunct Sci, Shinagawa Ku, Tokyo, Japan
[9] Hoshi Univ, Inst Adv Life Sci, Shinagawa Ku, Tokyo, Japan
[10] Toranomon Gen Hosp, Endocrine Ctr, Div Endocrinol, Minato Ku, Tokyo, Japan
[11] Ehime Univ, Grad Sch Med, Dept Pathophysiol, Toon, Ehime, Japan
来源
JOURNAL OF CLINICAL INVESTIGATION | 2022年 / 132卷 / 11期
基金
日本学术振兴会;
关键词
DNA METHYLOME SIGNATURE; WIDE ASSOCIATION; T-CELLS; METHYLATION; HYPOMETHYLATION; PROLIFERATION; RECOGNITION; INHIBITION; ACTIVATION; MATURATION;
D O I
10.1172/JCI150533
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页数:17
相关论文
共 50 条
  • [1] Epigenetic regulator, Uhrf1, positively controls skeletal muscle differentiation
    Sawada, Yuichiro
    Kikugawa, Tadahiko
    Sakakibara, Iori
    Ono, Yusuke
    Yanagihara, Yuta
    Saeki, Noritaka
    Iio, Hiroyuki
    Saika, Takashi
    Imai, Yuuki
    JOURNAL OF BONE AND MINERAL RESEARCH, 2018, 33 : 86 - 86
  • [2] Epigenetic regulator UHRF1 inactivates REST and growth suppressor gene expression via DNA methylation to promote axon regeneration
    Oh, Young Mi
    Mahar, Marcus
    Ewan, Eric E.
    Leahy, Kathleen M.
    Zhao, Guoyan
    Cavalli, Valeria
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (52) : E12417 - E12426
  • [3] UHRF1: a jack of all trades, and a master epigenetic regulator during spermatogenesis
    Newkirk, Simon J.
    An, Wenfeng
    BIOLOGY OF REPRODUCTION, 2020, 102 (06) : 1147 - 1152
  • [4] The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells
    Yuuki Obata
    Yukihiro Furusawa
    Takaho A Endo
    Jafar Sharif
    Daisuke Takahashi
    Koji Atarashi
    Manabu Nakayama
    Satoshi Onawa
    Yumiko Fujimura
    Masumi Takahashi
    Tomokatsu Ikawa
    Takeshi Otsubo
    Yuki I Kawamura
    Taeko Dohi
    Shoji Tajima
    Hiroshi Masumoto
    Osamu Ohara
    Kenya Honda
    Shohei Hori
    Hiroshi Ohno
    Haruhiko Koseki
    Koji Hase
    Nature Immunology, 2014, 15 : 571 - 579
  • [5] The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells
    Obata, Yuuki
    Furusawa, Yukihiro
    Endo, Takaho A.
    Sharif, Jafar
    Takahashi, Daisuke
    Atarashi, Koji
    Nakayama, Manabu
    Onawa, Satoshi
    Fujimura, Yumiko
    Takahashi, Masumi
    Ikawa, Tomokatsu
    Otsubo, Takeshi
    Kawamura, Yuki I.
    Dohi, Taeko
    Tajima, Shoji
    Masumoto, Hiroshi
    Ohara, Osamu
    Honda, Kenya
    Hori, Shohei
    Ohno, Hiroshi
    Koseki, Haruhiko
    Hase, Koji
    NATURE IMMUNOLOGY, 2014, 15 (06) : 571 - 579
  • [6] Stabilization of UHRF1 in synovial fibroblasts is a novel therapeutic strategy for rheumatoid arthritis.
    Saeki, Noritaka
    Inoue, Kazuki
    Ideta-Otsuka, Maky
    Watamori, Kunihiko
    Mizuki, Shinichi
    Takenaka, Katsuto
    Igarashi, Katsuhide
    Miura, Hiromasa
    Imai, Yuuki
    JOURNAL OF BONE AND MINERAL RESEARCH, 2022, 37 : 187 - 188
  • [7] UHRF1 Controls Thymocyte Fate Decisions Through the Epigenetic Regulation of EGR1 Expression
    Zhang, Yiwen
    Chen, Yingshi
    Ma, Rong
    Wei, Lai
    Zhang, Hui
    JOURNAL OF IMMUNOLOGY, 2020, 204 (01):
  • [8] UHRF1 Controls Thymocyte Fate Decisions through the Epigenetic Regulation of EGR1 Expression
    Zhang, Yiwen
    Chen, Yingshi
    Ma, Rong
    Jiang, Yawen
    Liu, Jun
    Lin, Yingtong
    Chen, Siqi
    Xia, Mengying
    Zou, Fan
    Zhang, Junsong
    Pan, Ting
    Wang, Lie
    Wei, Lai
    Zhang, Hui
    JOURNAL OF IMMUNOLOGY, 2020, 204 (12): : 3248 - 3261
  • [9] Negative modulation of the epigenetic regulator, UHRF1, by thyroid hormone receptors suppresses liver cancer cell growth
    Wu, Sheng-Ming
    Cheng, Wan-Li
    Liao, Chia-Jung
    Chi, Hsiang-Cheng
    Lin, Yang-Hsiang
    Tseng, Yi-Hsin
    Tsai, Chung-Ying
    Chen, Ching-Ying
    Lin, Syuan-Ling
    Chen, Wei-Jan
    Yeh, Yung-Hsin
    Huang, Chi-Ying F.
    Chen, Ming-Huang
    Yeh, Yi-Chen
    Lin, Kwang-Huei
    INTERNATIONAL JOURNAL OF CANCER, 2015, 137 (01) : 37 - 49
  • [10] Role of the Epigenetic Regulator EZH2 in Proinflammatory Macrophage Polarization and Signaling in Rheumatoid Arthritis
    Trenkmann, Michelle
    Linehan, Eimear
    Canavan, Mary
    Veale, Douglas J.
    Fearon, Ursula
    ARTHRITIS & RHEUMATOLOGY, 2015, 67