A critical role of transcription factor YY1 in rheumatoid arthritis by regulation of interleukin-6
A critical role of transcription factor YY1 in rheumatoid arthritis by regulation of interleukin-6
复制标题
转录因子 YY1 通过调节 IL-6 在类风湿性关节炎中发挥关键作用
DOI：
10.1016/j.jaut.2016.10.008
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发表时间：
2017-02-01
影响因子：
12.8
通讯作者：
Ou, Qishui
中科院分区：
文献类型：
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作者：
Lin, Jinpiao;He, Yujue;Ou, Qishui
先前的研究已经揭示了YY1（一种“阴阳”转录因子）在癌症发生和进展中的关键作用。然而，YY1在类风湿关节炎（RA）中是否有任何作用尚不清楚。本研究旨在探讨YY1在RA发病机制中的潜在作用。在本研究中，我们发现YY1在RA患者和CIA小鼠中过表达。用YYI shRNA慢病毒阻断YY1的作用可改善CIA小鼠的疾病进展。我们进一步通过匠心途径分析（ingenuity pathway analysis， IPA）分析了所涉及的信号通路，结果显示LV-YY1-shRNA处理显著抑制了IL-6信号通路和JAK/Stat信号通路。此外，我们观察到YY1的阻断减少了IL-6的产生并下调了Th17的数量。最后，我们发现YY1通过结合IL-6基因的启动子区来正向调节IL-6的转录。综上所述，YY1在RA中促进IL-6转录发挥关键作用，IL-6通过刺激Th17分化参与RA炎症。因此，YY1可能是参与RA炎症过程的关键分子。靶向YY1可能是治疗类风湿性关节炎的新策略。(C) 2016 Elsevier Ltd.版权所有。
Previous studies have revealed a critical role of YY1, a "Yin Yang" transcription factor, in cancer development and progression. However, whether YY1 has any role in rheumatoid arthritis (RA) remains unknown. This study aims to explore the potential role of YY1 in RA pathogenesis. In this study, we found that YY1 was over-expressed in RA patients and CIA mice. Blocking of YY1 action with YYI shRNA lentivirus ameliorated disease progression in CIA mice. We further analyzed the signaling pathway involved by ingenuity pathway analysis (IPA), results showed IL-6 signaling and JAK/Stat signaling pathway was significantly inhibited by LV-YY1-shRNA treatment. Moreover, we observed that blocking of YY1 reduced IL-6 production and downregulated Th17 population. Finally, we showed YY1 positively regulated IL-6 transcription by binding to the promoter region of the IL-6 gene. In conclusion, YY1 plays a critical role in promoting IL-6 transcription in RA which contribute to the inflammation of RA via stimulation of Th17 differentiation. Thus, YY1 is likely a key molecule involved in the inflammation process of RA. Targeting of YY1 may be a novel therapeutic strategy for RA. (C) 2016 Elsevier Ltd. All rights reserved.