On Mar. 26th 2018, the world famous Journal: Antioxidants and Redox Signaling (5-Year Impact Factor=7.087) online published the work from Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University entitled “Wnt signaling activates TIGAR and protects against cisplatin-induced spiral ganglion neuron damage in the mouse cochlea”. Prof. Renjie Chai from Southeast University and Prof. Haibo Wang from Shandong University is the co-corresponding authors for this manuscripts.
Cisplatin can damage spiral ganglion neurons (SGNs) and cause sensorineural hearing loss. Wnt activation protects against neomycin-induced hair cell damage in the mouse cochlea,but the role of Wnt signaling in protecting SGNs from cisplatin treatment has not yet been elucidated. This study was designed to investigate the neuroprotective effects of Wnt signaling against cisplatin-induced SGN damage. Firstly, we found that Wnt signaling was activated in SGNs after cisplatin treatment. Next, we discovered that overexpression of Wnt signaling in SGNs reduced cisplatin-induced SGN loss by inhibiting Caspase-associated apoptosis, thus preventing the loss of SGN function after cisplatin treatment. In contrast, inhibition of Wnt signaling increased apoptosis, made SGNs more vulnerable to cisplatin treatment, and exacerbated hearing loss. TP53-induced glycolysis and apoptosis regulator (TIGAR), which scavenges intracellular reactive oxygen species (ROS), was upregulated in SGNs in response to cisplatin administration. Wnt/β-catenin activation increased TIGAR expression and reduced ROS level, while inhibition of Wnt/β-catenin in SGNs reduced TIGAR expression and increased the ROS level. Moreover,overexpression of TIGAR reduced ROS and decreased Caspase 3 expression as well as increased the survival of SGNs in Wnt-inhibited SGNs. Lastly, antioxidant treatment rescued the more severe SGN loss induced by β-catenin deficiency after cisplatin treatment. This study is the first to indicate that Wnt signaling activates TIGAR and protects SGNs against cisplatin-induced damage through the inhibition of oxidative stress and apoptosis in SGNs, and this might offer novel therapeutic targets for the prevention of SGN injury.
