Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan 250022, China.
Biomed Res Int. 2019 Oct 7;2019:7878906. doi: 10.1155/2019/7878906. eCollection 2019.
It has been reported that paclitaxel administration could cause sensorineural hearing loss, and Wnt activation is important for the development and cell protection of mouse cochlea. However, the effect of Wnt signaling in spiral ganglion neurons (SGNs) damage induced by paclitaxel has not yet been elucidated. In this study, we explored the effect of paclitaxel on SGNs in the mouse cochlea and the neuroprotective effects of Wnt signaling pathway against paclitaxel-induced SGN damage by using Wnt agonist/antagonists . We first found that paclitaxel treatment resulted in a degenerative change and reduction of cell numbers in SGNs and induced caspase-mediated apoptosis in SGNs. The expression levels of -catenin and C-myc were increased, thus indicating Wnt signaling was activated in SGNs after paclitaxel treatment. The activation of Wnt signaling pathway protected against SGN loss after exposure to paclitaxel, whereas the suppression of Wnt signaling in SGNs made them more vulnerable to paclitaxel treatment. We also showed that activation of Wnt signaling in SGNs inhibited caspase-mediated apoptosis. Our findings demonstrated that Wnt signaling had an important role in protecting SGNs against paclitaxel-induced damage and thus might be an effective therapeutic target for the prevention of paclitaxel-induced SGN death.
已有报道称紫杉醇给药可导致感音神经性听力损失，Wnt 激活对于小鼠耳蜗的发育和细胞保护很重要。然而，紫杉醇诱导的螺旋神经节神经元（SGNs）损伤中 Wnt 信号通路的作用尚未阐明。在这项研究中，我们通过使用 Wnt 激动剂/拮抗剂探讨了紫杉醇对小鼠耳蜗 SGNs 的影响，以及 Wnt 信号通路对紫杉醇诱导的 SGN 损伤的神经保护作用。我们首先发现紫杉醇处理导致 SGNs 发生退行性变化和数量减少，并诱导 SGNs 中的半胱天冬酶介导的细胞凋亡。β-catenin 和 C-myc 的表达水平增加，表明紫杉醇处理后 SGNs 中 Wnt 信号被激活。Wnt 信号通路的激活可防止暴露于紫杉醇后 SGN 的丢失，而 SGN 中 Wnt 信号的抑制则使它们更容易受到紫杉醇处理的影响。我们还表明，SGNs 中 Wnt 信号的激活抑制了半胱天冬酶介导的细胞凋亡。我们的研究结果表明，Wnt 信号在保护 SGNs 免受紫杉醇诱导的损伤方面发挥着重要作用，因此可能成为预防紫杉醇诱导的 SGN 死亡的有效治疗靶点。
