摘要
Although cisplatin is a widely used chemotherapeutic agent,it is severely toxic and causes irreversible hearing loss,restricting its application in clinical settings.This study aimed to determine the molecular mechanism underlying cisplatin-induced ototoxicity.Here,we established in vitro and in vivo ototoxicity models of cisplatininduced hair cell loss,and our results showed that reducing STING levels decreased inflammatory factor expression and hair cell death.In addition,we found that cisplatin-induced mitochondrial dysfunction was accompanied by cytosolic DNA,which may act as a critical linker between the cyclic GMP-AMP synthesis−stimulator of interferon genes(cGASSTING)pathway and the pathogenesis of cisplatin-induced hearing loss.H-151,a specific inhibitor of STING,reduced hair cell damage and ameliorated the hearing loss caused by cisplatin in vivo.This study underscores the role of cGASSTING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.
基金
supported by grants from the National Natural Science Foundation of China(82222017,82271183,and 81970883)
the Key Research and Development Program of Hubei Province(2022BCA046)
funding from the Fundamental Research Funds for the Central Universities(2042022kf0059).
