Evidence for regulatory diversity and auto-regulation at the TAC1 locus in sensory neurones.
Evidence for regulatory diversity and auto-regulation at the TAC1 locus in sensory neurones.
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DOI：
10.1186/1742-2094-8-10
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发表时间：
2011-02-04
影响因子：
9.3
通讯作者：
MacKenzie A
中科院分区：
文献类型：
--
作者：
Shanley L;Lear M;Davidson S;Ross R;MacKenzie A
神经肽物质-P (SP) 由感觉神经元中的 TAC1 基因表达，充当神经源性炎症的关键调节剂。 TAC1 的启动子 (TAC1prom) 在 TAC1 基因的调控中发挥核心作用，但需要第二个调控元件的存在； ECR2，支持感觉神经元中的 TAC1 表达，并对信号通路（如 MAP 激酶和辣椒素的有害诱导）做出适当的反应。我们检查了辣椒素对较大直径神经元中 ECR2-TAC1prom 活性的影响是细胞自主的还是非细胞自主的。我们证明TRPV1在辣椒素诱导后并不在所有与SP相同的细胞中表达，这表明在辣椒素诱导后存在TAC1上调的非细胞自主机制。此外，我们证明这些较大直径的神经元中 SP 和 ECR1-TAC1prom 活性的诱导可以通过钾去极化来诱导，这表明除了辣椒素诱导之外，转基因活性还可以通过电压门控钙通道来调节。此外，我们表明，在辣椒素诱导后，NK1在所有表达SP的细胞中表达，并且NK1的激动剂可以激活较大直径神经元中的SP和转基因。这些观察结果表明，感觉神经元中存在控制 TAC1 启动子表达的自分泌环。相反，LPS 对 TAC1 启动子的诱导不依赖于 ECR2，并且不会发生在大直径神经元中。这些研究证明了调节 TAC1 启动子活性的机制的多样性，并为开发新的抗炎疗法提供了新的方向。
The neuropeptide substance-P (SP) is expressed from the TAC1 gene in sensory neurones where it acts as a key modulator of neurogenic inflammation. The promoter of TAC1 (TAC1prom) plays a central role in the regulation of the TAC1 gene but requires the presence of a second regulatory element; ECR2, to support TAC1 expression in sensory neurones and to respond appropriately to signalling pathways such as MAPkinases and noxious induction by capsaicin. We examined whether the effect of capsaicin on ECR2-TAC1prom activity in larger diameter neurones was cell autonomous or non- cell autonomous. We demonstrate that TRPV1 is not expressed in all the same cells as SP following capsaicin induction suggesting the presence of a non-cell autonomous mechanism for TAC1 up-regulation following capsaicin induction. In addition, we demonstrate that induction of SP and ECR1-TAC1prom activity in these larger diameter neurones can be induced by potassium depolarisation suggesting that, in addition to capsaicin induction, transgene activity may be modulated by voltage gated calcium channels. Furthermore, we show that NK1 is expressed in all SP- expressing cells after capsaicin induction and that an agonist of NK1 can activate both SP and the transgene in larger diameter neurones. These observations suggest the presence of an autocrine loop that controls the expression of the TAC1 promoter in sensory neurones. In contrast, induction of the TAC1 promoter by LPS was not dependent on ECR2 and did not occur in large diameter neurones. These studies demonstrate the diversity of mechanisms modulating the activity of the TAC1 promoter and provide novel directions for the development of new anti-inflammatory therapies.
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影响因子：
4.2
作者：
Hou, LF;Wang, X
通讯作者：
Wang, X
影响因子：
5.5
作者：
DONALDSON, LF;MCQUEEN, DS;SECKL, JR
通讯作者：
SECKL, JR
影响因子：
2.5
作者：
Garrett, NE;Cruwys, SC;Tomlinson, DR
通讯作者：
Tomlinson, DR
DOI：
10.1016/j.molbrainres.2005.03.015
发表时间：
2005-07-29
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Boer, PA;Ueno, M;Gontijo, JAR
通讯作者：
Gontijo, JAR
DOI：
10.1165/rcmb.2002-0107oc
发表时间：
2003-11-01
影响因子：
6.4
作者：
Huang, HY;Lai, YL
通讯作者：
Lai, YL