...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Inhibition of DNA methyltransferase-1 instigates the expression of DNA methyltransferase-3a in angioplasty-induced restenosis
【24h】

Inhibition of DNA methyltransferase-1 instigates the expression of DNA methyltransferase-3a in angioplasty-induced restenosis

机译：DNA甲基转移酶-1的抑制唤起DNA甲基转移酶-3A在血管成形术诱导的再狭窄中的表达

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

Increased expression of DNA methyltransferase-1 (DNMT1) associates with the progression of many human diseases. Because DNMT1 induces cell proliferation, drugs that inhibit DNMT1 have been used to treat proliferative diseases. Because these drugs are nonspecific inhibitors of DNMT1, subsidiary events or the compensatory mechanisms that are activated in the absence of DNMT1 limit their therapeutic application. Here, we studied the molecular mechanisms that occur during angioplasty-induced restenosis and found that DNMT1 inhibition in both in vitro and in vivo approaches resulted in the induction of DNA methyltransferase-3a (DNMT3a) expression. In vascular smooth muscle cells (VSMCs), the microRNA hsa-miR-1264 mimic, specifically inhibiting DNMT1, induced nuclear expression of DNMT3a. On the contrary, there was no induced expression of DNMT3a in VSMCs that were transfected with hsa-miR-1264 inhibitor. Further, ectopic expression of suppressor of cytokine signaling 3 (SOCS3) through adeno-associated virus (AAV)-mediated gene delivery in the coronary arteries of Yucatan microswine showed inhibition of both DNMT1 and DNMT3a in vivo. These findings show the existence of an inter-regulatory mechanism between DNMT1 and DNMT3a where, in the absence of DNMT1, induction of DNMT3a compensates for the loss of DNMT1 functions, suggesting that the inhibition of both DNMT1 and DNMT3a are required to prevent restenosis.
机译：增加DNA甲基转移酶-1（DNMT1）与许多人类疾病的进展的表达。因为DNMT1诱导细胞增殖，所以抑制DNMT1的药物已被用于治疗增殖性疾病。因为这些药物是DNMT1，辅助事件或在不存在DNMT1的情况下激活的补偿机制的非特异性抑制剂，所以在没有DNMT1限制其治疗方法的情况下。在这里，我们研究了在血管成形术诱导的再狭窄期间发生的分子机制，发现在体外和体内方法中的DNMT1抑制导致DNA甲基转移酶-3a（DNMT3A）表达的诱导。在血管平滑肌细胞（VSMC）中，MicroRNA HSA-miR-1264模拟，特别抑制DNMT1，诱导DNMT3A的核表达。相反，没有用HSA-miR-1264抑制剂转染的VSMC中DNMT3A的诱导表达。此外，通过腺苷相关病毒（AAV）抑制细胞因子信号传导3（SOCS3）的异位表达在尤卡坦的微血症冠状动脉中介导的基因递送显示抑制DNMT1和DNMT3A在体内的抑制作用。这些发现显示DNMT1和DNMT3A之间的调节间机制的存在，其中在不存在DNMT1的情况下，DNMT3A的诱导补偿DNMT1功能的损失，表明DNMT1和DNMT3A的抑制是需要防止再狭窄的抑制。

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