ErbB4 protects against neuronal apoptosis via activation of YAP/PIK3CB signaling pathway in a rat model of subarachnoid hemorrhage
ErbB4 protects against neuronal apoptosis via activation of YAP/PIK3CB signaling pathway in a rat model of subarachnoid hemorrhage
复制标题
ErbB4 通过激活 YAP/PIK3CB 信号通路在大鼠蛛网膜下腔出血模型中防止神经元凋亡
DOI：
10.1016/j.expneurol.2017.07.014
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发表时间：
2017-11-01
影响因子：
5.3
通讯作者：
Zhang, John H.
中科院分区：
文献类型：
--
作者：
Yan, Feng;Tan, Xiaoxiao;Zhang, John H.
神经元凋亡是蛛网膜下腔出血（SAH）早期脑损伤的重要病理过程。先前的研究表明，ErbB 4（EGFR家族成员v-erb-b2禽成红细胞白血病病毒癌基因同源物4）对神经系统的正常发育和维持至关重要。在本研究中，我们探讨了ErbB 4及其下游的雅普（是相关蛋白）/PIK 3CB信号通路在大鼠模型SAH后早期脑损伤中的神经保护作用。于SAH后24 h和72 h采用改良Garcia量表和平衡木平衡试验对大鼠进行神经功能评价。使用ErbB 4激活剂神经调节蛋白1 β 1（Nrg 1 β 1）、ErbB 4 siRNA和雅普siRNA来探索该途径。SAH后p-ErbB 4和雅普的表达明显增加。多项免疫荧光标记实验证实ErbB 4主要在神经元中表达。ErbB 4及其下游信号的激活改善了SAH后的神经功能缺损，并显着减少了神经元细胞死亡。抑制ErbB 4可降低雅普和PIK 3CB的表达，并加重细胞凋亡。雅普敲低降低了PIK 3CB水平并消除了ErbB 4活化的抗凋亡作用。提示ErbB 4可能通过雅普/PIK 3CB信号通路在SAH后早期脑损伤中发挥神经保护作用。
Neuronal apoptosis is a central pathological process in subarachnoid hemorrhage (SAH)-induced early brain injury. Previous studies indicated that ErbB4 (EGFR family member v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) is essential for normal development and maintenance of the nervous system. In this study, we explored the neuroprotective effects of ErbB4 and its downstream YAP (yes-associated protein)/PIK3CB signaling pathway in early brain injury after SAH in a rat model using the endovascular perforation method. Rats were neurologically evaluated with the Modified Garcia Scale and beam balance test at 24 h and 72 h after SAH. An ErbB4 activator Neuregulin 1 beta 1 (Nrg 1 beta 1), ErbB4 siRNA and YAP siRNA were used to explore this pathway. The expression of p-ErbB4 and YAP was significantly increased after SAH. Multiple immunofluorescence labeling experiments demonstrated that ErbB4 is mainly expressed in neurons. Activation of ErbB4 and its downstream signals improved the neurological deficits after SAH and significantly reduced neuronal cell death. Inhibition of ErbB4 reduced YAP and PIK3CB expression, and aggravated cell apoptosis. YAP knockdown reduced the PIK3CB level and eliminated the anti-apoptotic effects of ErbB4 activation. These findings indicated that ErbB4 plays a neuroprotective role in early brain injury after SAH, possibly via the YAP/PIK3CB signaling pathway.