Spinal expression of Hippo signaling components YAP and TAZ following peripheral nerve injury in rats.

Spinal expression of Hippo signaling components YAP and TAZ following peripheral nerve injury in rats.
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DOI:
10.1016/j.brainres.2013.08.049
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发表时间:
2013-10-16
期刊:
影响因子:
2.9
通讯作者:
Mao J
Mao J
中科院分区:
医学3区
文献类型:
--
作者:
Li N;Lim G;Chen L;McCabe MF;Kim H;Zhang S;Mao J

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以往的研究表明,周围神经损伤后脊髓背角细胞的形态和数量会发生变化,Hippo信号通路在细胞生长、增殖、凋亡和树突重塑中起着重要作用。在本研究中,我们研究了雅普和TAZ的表达,两个重要的组成部分调节Hippo信号,在脊髓背角是否会改变慢性压迫坐骨神经损伤(CCI)。我们发现:1)雅普主要表达在CGRP和IB 4免疫反应的初级传入神经末梢上,在胶质细胞上没有明显表达,而TAZ主要表达在脊髓二级神经元和小胶质细胞上;(2)CCI后雅普和TAZ表达上调有两种不同的时间模式,其中雅普和TAZ的最高表达出现在CCI后第14天和第1天,分别为:3)雅普和TAZ在脊髓背角的分布也有其独特的地形图模式,这与它们与初级传入和二级神经元的独特联系相一致:4)雅普表达的变化选择性地由CCI而不是CFA诱导的后爪炎症引起; 5)CCI后TAZ表达的细胞核数目明显增多,表明TAZ从细胞质向细胞核转位。这些结果表明,周围神经损伤诱导脊髓雅普和TAZ表达的时间依赖性和区域特异性变化。海马信号在突触和结构可塑性的作用进行了讨论有关神经病理性疼痛的细胞机制。
Previous studies have shown that the morphology and number of cells in the spinal cord dorsal horn could change following peripheral nerve injury and that the Hippo signaling pathway plays an important role in cell growth, proliferation, apoptosis, and dendritic remolding. In the present study, we examined whether the expression of YAP and TAZ, two critical components regulated by Hippo signaling, in the spinal cord dorsal horn would be altered by chronic constriction sciatic nerve injury (CCI). We found that 1) YAP was mainly expressed on CGRP- and IB4-immunoreactive primary afferent nerve terminals without noticeable expression on glial cells, whereas TAZ was mainly expressed on spinal cord second order neurons as well as microglia; 2) upregulation of YAP and TAZ expression followed two distinct temporal patterns after CCI, such that the highest expression of YAP and TAZ was on day 14 and day 1 after CCI, respectively; 3) there were also unique topographic patterns of YAP and TAZ distribution in the spinal cord dorsal horn consistent with their distinctive association with primary afferents and second order neurons; 4) changes in the YAP expression were selectively induced by CCI but not CFA-induced hindpaw inflammation; and 5) the number of nuclear profiles of TAZ expression was significantly increased after CCI, indicating translocation of TAZ from the cytoplasma to nucleus. These findings indicate that peripheral nerve injury induced time-dependent and region-specific changes in the spinal YAP and TAZ expression. A role for Hippo signaling in synaptic and structural plasticity is discussed in relation to the cellular mechanism of neuropathic pain.
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