...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >N6-methyladenosine demethylase FTO promotes M1 and M2 macrophage activation
【24h】

N6-methyladenosine demethylase FTO promotes M1 and M2 macrophage activation

机译：N6-甲基碳苷脱甲基酶FTO促进M1和M2巨噬细胞活化

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Macrophage polarization is the driving force of various inflammatory diseases, especially those involved in M1/M2 imbalance. N6-methyladenosine (m(6)A) is the most prevalent internal mRNA modification in eukaryotes that affects multiple biological processes, including those involved developmental arrest and immune response. However, the role of m(6)A in macrophage polarization remains unclear. This study found that FTO silencing significantly suppressed both M1 and M2 polarization. FTO depletion decreased the phosphorylation levels of IKK alpha/beta, I kappa B alpha and p65 in the NF-kappa B signaling pathway. The expression of STAT1 was downregulated in M1-polarized macrophages while the expression of STAT6 and PPAR-gamma decreased in M2 polarization after FTO knockdown. The actinomycin D experiments showed that FTO knockdown accelerated mRNA decay of STAT1 and PPAR-gamma. Furthermore, the stability and expression of STAT1 and PPAR-gamma mRNAs increased when the m6A reader YTHDF2 was silenced. In conclusion, our results suggest that FTO knockdown inhibits the NF-kappa B signaling pathway and reduces the mRNA stability of STAT1 and PPAR-gamma via YTHDF2 involvement, thereby impeding macrophage activation. These findings indicated a previously unrecognized link between FTO and macrophage polarization and might open new avenues for research into the molecular mechanisms of macrophage polarization-related diseases.
机译：巨噬细胞极化是各种炎症疾病的驱动力，尤其是参与M1 / M2失衡的驱动力。 N6-甲基腺苷（M（6）A）是影​​响多种生物学过程的真核生物中最普遍的内部mRNA改性，包括参与发展逮捕和免疫应答。然而，M（6）A在巨噬细胞极化中的作用仍不清楚。本研究发现，FTO沉默显着抑制了M1和M2极化。 FTO耗尽降低了NF-Kappa信令通路中IKKα/β，IκBα和P65的磷酸化水平。在F1-偏振巨噬细胞中，Dat1的表达在M1-偏振巨噬细胞中下调，在FTO敲击后M2偏振中的表达降低。放线菌素D实验表明，STAT1和PPAR-GAMMA的FTO敲速加速mRNA衰减。此外，当M6A读取器Ythdf2沉默时，STAT1和PPAR-Gamma MRNA的稳定性和表达增加。总之，我们的研究结果表明FTO敲低抑制NF-Kappa B信号通路，并通过YTHDF2受累降低Stat1和PPAR-Gamma的mRNA稳定性，从而阻碍巨噬细胞激活。这些发现表明FTO和巨噬细胞极化之间的先前未被识别的联系，并且可能开辟了新的途径，用于研究巨噬细胞偏振相关疾病的分子机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号