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...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.展开更多
基金supported by the National Natural Science Foundation of China(No.81771020,81570927 and 81271092)Grant for Scientific and Technological Development Plan for Medical and Health in Shandong Province(2019WS341).
文摘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.
