Departments of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
Departments of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi, PR China.
Neurosci Lett. 2021 Apr 23;751:135803. doi: 10.1016/j.neulet.2021.135803. Epub 2021 Mar 8.
Sensorineural hearing loss (SNHL) is a common causes of disability. Neural stem cells (NSCs) from the cochlear nuclei have been considered to be a potential direction for the treatment of SNHL. Neuregulin 1 (NRG1)/ErbB2 signaling displays an essential role in nervous system development. In this study, we aimed to explore the roles of NRG1/ErbB2 in differentiation and apoptosis of cochlear nuclei NSCs. The data showed that the expression of NGR1 and ErbB2 in cochlear nuclei NSCs isolated from rats were increased with the age of rats. NRG1 treatment reduced the nestin-positive cells number, increased the MAP2-positive and GFAP-positive cells number, decreased the expression of cleaved-caspase-3, and increased the activation of PI3K/AKT. ErbB2 knockdown by lentiviral-mediated ErbB2 shRNA infection reversed the effect of NRG1 on cochlear nuclei NSCs. LY294002 administration further enhanced the effect of ErbB2 silencing on the expression of nestin, MAP2, GFAP and cleaved-caspase-3. Taken together, NRG1/ErbB2 regulates differentiation and apoptosis of cochlear nucleus NSCs through PI3K/Akt pathway.
感音神经性听力损失(SNHL)是一种常见的残疾原因。耳蜗核中的神经干细胞(NSCs)被认为是治疗 SNHL 的潜在方向。神经调节蛋白 1(NRG1)/表皮生长因子受体 2(ErbB2)信号在神经系统发育中起着重要作用。在这项研究中,我们旨在探讨 NRG1/ErbB2 在耳蜗核 NSCs 分化和凋亡中的作用。数据显示,从大鼠耳蜗核分离的 NSCs 中 NRG1 和 ErbB2 的表达随着大鼠年龄的增加而增加。NRG1 处理减少了巢蛋白阳性细胞数量,增加了 MAP2 阳性和 GFAP 阳性细胞数量,降低了 cleaved-caspase-3 的表达,并激活了 PI3K/AKT。通过慢病毒介导的 ErbB2 shRNA 感染沉默 ErbB2 逆转了 NRG1 对耳蜗核 NSCs 的作用。LY294002 进一步增强了 ErbB2 沉默对巢蛋白、MAP2、GFAP 和 cleaved-caspase-3 表达的影响。总之,NRG1/ErbB2 通过 PI3K/Akt 通路调节耳蜗核 NSCs 的分化和凋亡。