...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Molecular basis for keratoconus: lack of TrkA expression and its transcriptional repression by Sp3.
【24h】

Molecular basis for keratoconus: lack of TrkA expression and its transcriptional repression by Sp3.

机译：圆锥角膜的分子基础：缺乏TrkA表达及其被Sp3转录抑制。

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

Keratoconus is the most common corneal dystrophy that leads to severe visual impairment. Although the major etiological factors are genetic, the pathogenetic mechanism(s) is unknown. No medical treatments exist, and the only therapeutic approach is corneal transplantation. Recent data demonstrate the involvement of nerve growth factor (NGF) in trophism and corneal wound healing. In this study, we investigated alterations in the NGF pathway in keratoconus-affected corneas and found a total absence of the NGF-receptor TrkA (TrkA(NGFR)) expression and a decreased expression of NGF and p75(NTR). The absence of TrkA(NGFR) expression was associated with a strong increase in the Sp3 repressor short isoform(s) and a lack of the Sp3 activator long isoform. Sp3 is a bifunctional transcription factor that has been reported to stimulate or repress the transcription of numerous genes. Indeed, we found that Sp3 short isoform(s) overexpression in cell culture results in a down-regulation of TrkA(NGFR) expression. We suggest that an imbalance in Sp transcription-factor isoforms may play a role in controlling the NGF signaling, thus contributing to the pathogenesis of keratoconus. This mechanism for the transcriptional repression of the TrkA(NGFR) gene can provide the platform for the development of a therapeutic strategy.
机译：圆锥角膜是最常见的角膜营养不良，会导致严重的视力障碍。尽管主要病因是遗传的，但其致病机理尚不清楚。目前尚无药物治疗，唯一的治疗方法是角膜移植。最近的数据表明神经生长因子（NGF）参与营养和角膜伤口愈合。在这项研究中，我们调查了圆锥角膜感染的角膜中NGF途径的变化，发现NGF受体TrkA（TrkA（NGFR））的表达完全不存在，而NGF和p75（NTR）的表达却降低了。 TrkA（NGFR）表达的缺乏与Sp3阻遏物短同种型的强烈增加和Sp3激活剂长同种型的缺乏有关。 Sp3是一种双功能转录因子，据报道可刺激或抑制众多基因的转录。确实，我们发现细胞培养中的Sp3短异构体过度表达导致TrkA（NGFR）表达的下调。我们建议Sp转录因子同工型的失衡可能在控制NGF信号传导中起作用，从而有助于圆锥角膜的发病。 TrkA（NGFR）基因的转录抑制的这种机制可以为发展治疗策略提供平台。

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