Loss of Fascin2 increases susceptibility to cisplatin-induced hearing impairment and cochlear cell apoptosis in mice

Author:

Wang Yan1,Liu Yingying1,Xie Yi1,Luan Jun1,Liu Rongrong1,Zhu Yongjia1,Ma Ying1,Fan Yi1,Sun Yan2,Shang Wenjing1,Han Fengchan1

Affiliation:

1. Binzhou Medical University

2. Affiliated Yantai Yuhuangding Hospital of Qingdao University

Abstract

Abstract Objectives. Deletion of Fscn2 gene in mice has been linked to progressive hearing loss and degeneration of cochlear cells. Cisplatin, an antitumor drug, can cause various side effects, including ototoxicity. The aim of this study was to investigate the effects of Fscn2 on cisplatin-induced hearing impairment in mice and to explore the possible mechanism. Methods. Two-week-old Fscn2+/+ mice and Fscn2-/- mice were treated with two doses of cisplatin, with a 3-day recovery period in between. ABR (auditory evoked brain stem response) thresholds were measured and cochlear pathology was observed at 3 weeks of age. Results. Both Fscn2+/+ and Fscn2-/- mice showed hearing loss under the effect of cisplatin, but the impairment was more severe in Fscn2-/- mice. Further experiments showed that the percentages of outer hair cell (OHC) and spiral ganglion neuron (SGN) loss were significantly higher in cisplatin-treated Fscn2-/- mice compared to Fscn2+/+ mice. Additionally, knockdown of Fscn2 in HEI-OC1 cells worsened cisplatin-induced cell apoptosis. Conclusion. FSCN2 mediates reduction of CDDP induced ototoxicity by inhibiting cell apoptosis

Publisher

Research Square Platform LLC

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