Transcription of rat TRPV1 utilizes a dual promoter system that is positively regulated by nerve growth factor.
Transcription of rat TRPV1 utilizes a dual promoter system that is positively regulated by nerve growth factor.
复制标题
大鼠 TRPV1 的转录利用受神经生长因子正向调节的双启动子系统。
DOI：
10.1111/j.1471-4159.2006.04363.x
复制
发表时间：
2007
影响因子：
4.7
通讯作者：
Schumacher,MarkA
中科院分区：
文献类型：
--
作者：
Xue,Qing;Jong,Beverly;Chen,Tom;Schumacher,MarkA
辣椒素受体，也被称为瞬时受体电位香草样受体亚型1 (TRPV1, VR1)，是一种表达于初级传入伤害感受器中的离子通道亚基，在疼痛转导和热痛觉过敏中起关键作用。伤害感受器TRPV1 mRNA和蛋白的增加与组织损伤-炎症有关。由于人们对伤害感受器中TRPV1 RNA转录的控制机制知之甚少，因此我们对大鼠TRPV1基因的上游部分进行了功能表征。鉴定出两个功能性rTRPV1启动子区域及其转录起始位点。虽然这两个启动子区域在神经生长因子（NGF）处理的大鼠感觉神经元中指导转录活性，但上游的核心启动子在丰富的感觉神经元培养中最活跃。由于NGF是炎症性疼痛的关键调节剂，我们研究了NGF对PC12细胞中rTRPV1转录的影响。NGF正调控PC12细胞中两个rTRPV1启动子区域的转录活性。我们认为rTRPV1基因的上游调控区由一个双启动子系统组成，并受NGF调控。这些发现支持了在组织损伤和/或炎症条件下产生的NGF部分通过转录依赖机制指导伤害感受器中TRPV1表达的增加的假设。
The capsaicin receptor, also known as ‘transient receptor potential vanilloid receptor subtype 1’ (TRPV1, VR1), is an ion channel subunit expressed in primary afferent nociceptors, which plays a critical role in pain transduction and thermal hyperalgesia. Increases in nociceptor TRPV1 mRNA and protein are associated with tissue injury–inflammation. As little is understood about what controls TRPV1 RNA transcription in nociceptors, we functionally characterized the upstream portion of the rat TRPV1 gene. Two functional rTRPV1 promoter regions and their transcription initiation sites were identified. Although both promoter regions directed transcriptional activity in nerve growth factor (NGF) treated rat sensory neurons, the upstream Core promoter was the most active in cultures enriched in sensory neurons. Because NGF is a key modulator of inflammatory pain, we examined the effect of NGF on rTRPV1 transcription in PC12 cells. NGF positively regulated transcriptional activity of both rTRPV1 promoter regions in PC12 cells. We propose that the upstream regulatory region of the rTRPV1 gene is composed of a dual promoter system that is regulated by NGF. These findings support the hypothesis that NGF produced under conditions of tissue injury and/or inflammation directs an increase of TRPV1 expression in nociceptors in part through a transcription‐dependent mechanism.