Tumor necrosis factor receptor-associated factor 5 is an essential mediator of ischemic brain infarction
Tumor necrosis factor receptor-associated factor 5 is an essential mediator of ischemic brain infarction
复制标题
肿瘤坏死因子受体相关因子5是缺血性脑梗死的重要介质
DOI：
10.1111/jnc.12207
复制
发表时间：
2013-08-01
影响因子：
4.7
通讯作者：
Li, Hongliang
中科院分区：
文献类型：
--
作者：
Wang, Lang;Lu, Yanyun;Li, Hongliang
肿瘤坏死因子受体相关因子5（tumor necrosis factor receptor associated factor 5，TRAF 5）是肿瘤坏死因子受体（tumor necrosis factor receptor，TNF）超家族和白细胞介素1受体/Toll样受体（interleukin-1 receptor/Toll-like receptor，IL-1 receptor/Toll-like receptor）超家族的一个接头蛋白，在多种信号通路中发挥重要的调节作用。本研究旨在探讨TRAF 5在脑缺血/再灌注（I/R）损伤中的作用。在TRAF 5敲除小鼠（KO）、神经元特异性TRAF 5转基因（TG）和适当的对照组中进行大脑中动脉的短暂闭塞。与WT小鼠相比，TRAF 5 KO小鼠在神经系统测试中显示出更低的梗死体积和更好的结果。TRAF 5基因敲除小鼠表现出较低的神经元凋亡水平、减弱的血脑屏障（BBB）破坏和抑制的炎症反应。TRAF 5 TG小鼠表现出相反的表型。此外，Akt/FoxO 1信号通路在TRAF 5 KO小鼠的缺血脑中增强。这些结果首次证明TRAF 5是实验性中风模型中I/R损伤的关键介质。Akt /FoxO 1信号通路可能在TRAF 5的生物学功能中起重要作用。
Tumor necrosis factor receptor-associated factor 5 (TRAF5) is an adaptor protein of the tumor necrosis factor (TNF) receptor superfamily and the interleukin-1 receptor/Toll-like receptor superfamily and plays important roles in regulating multiple signaling pathways. This study was conducted to investigate the role of TRAF5 in the context of brain ischemia/reperfusion (I/R) injury. Transient occlusion of the middle cerebral artery was performed on TRAF5 knockout mice (KO), neuron-specific TRAF5 transgene (TG), and the appropriate controls. Compared with the WT mice, the TRAF5 KO mice showed lower infarct volumes and better outcomes in the neurological tests. A low neuronal apoptosis level, an attenuated blood-brain barrier (BBB) disruption and an inhibited inflammatory response were exhibited in TRAF5 KO mice. TRAF5 TG mice exhibited an opposite phenotype. Moreover, the Akt/FoxO1 signaling pathway was enhanced in the ischemic brains of the TRAF5 KO mice. These results provide the first demonstration that TRAF5 is a critical mediator of I/R injury in an experimental stroke model. The Akt /FoxO1 signaling pathway probably plays an important role in the biological function of TRAF5 in this model.