Inhibition of the cGAS‑STING Pathway Reduces Cisplatin-Induced Inner Ear Hair Cell Damage

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 cisplatin-induced 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 (cGAS-STING) 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 cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.

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Publication Details

Journal
Neuroscience Bulletin
Published
2024-12-16
DOI
https://doi.org/10.1007/s12264-024-01334-8
Citations
5
Primary Topic
interferon and immune responses
Type
article
Field-Weighted Citation Impact
1.20

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article

Inhibition of the cGAS‑STING Pathway Reduces Cisplatin-Induced Inner Ear Hair Cell Damage

Shan Xu, Haiying Sun, Xiaoxiang Xu, Mingliang Tang et al.
5 citations
Neuroscience Bulletin
interferon and immune responses
1.20
article

Inhibition of the cGAS‑STING Pathway Reduces Cisplatin-Induced Inner Ear Hair Cell Damage

Shan Xu, Haiying Sun, Xiaoxiang Xu, Mingliang Tang, Weijia Kong, Xiong Chen, Zuhong He, Ying Sun, Shengyu Zou
article en
5 citations

Abstract

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 cisplatin-induced 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 (cGAS-STING) 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 cGAS-STING in cisplatin ototoxicity and presents H-151 as a promising therapeutic for hearing loss.

Neuroscience BulletinVol. 41(3)
Union Hospital (HK), Wuhan University (CN), Soochow University (CN), Zhongda Hospital Southeast University (CN), Zhongnan Hospital of Wuhan University (CN), First Hospital of China Medical University (CN), State Key Laboratory of Digital Medical Engineering (CN), Huazhong University of Science and Technology (CN), Southeast University (CN), China Medical University (CN)
National Natural Science Foundation of China, Sun Yat-sen University, Fundamental Research Funds for the Central Universities
Good health and well-being
Openalex Percentile: Top 20%
interferon and immune responses
1.20
DOIOpen Access PDFOpenAlex
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