Suppression of the TGF-ß signaling exacerbates degeneration of auditory neurons in kanamycin-induced ototoxicity in mice.
Sci Rep
; 14(1): 10910, 2024 05 13.
Article
em En
| MEDLINE
| ID: mdl-38740884
ABSTRACT
Transforming growth factor-ß (TGF-ß) signaling plays a significant role in multiple biological processes, including inflammation, immunity, and cell death. However, its specific impact on the cochlea remains unclear. In this study, we aimed to investigate the effects of TGF-ß signaling suppression on auditory function and cochlear pathology in mice with kanamycin-induced ototoxicity. Kanamycin and furosemide (KM-FS) were systemically administered to 8-week-old C57/BL6 mice, followed by immediate topical application of a TGF-ß receptor inhibitor (TGF-ßRI) onto the round window membrane. Results showed significant TGF-ß receptor upregulation in spiral ganglion neurons (SGNs) after KM-FA ototoxicity, whereas expression levels in the TGF-ßRI treated group remained unchanged. Interestingly, despite no significant change in cochlear TGF-ß expression after KM-FS ototoxicity, TGF-ßRI treatment resulted in a significant decrease in TGF-ß signaling. Regarding auditory function, TGF-ßRI treatment offered no therapeutic effects on hearing thresholds and hair cell survival following KM-FS ototoxicity. However, SGN loss and macrophage infiltration were significantly increased with TGF-ßRI treatment. These results imply that inhibition of TGF-ß signaling after KM-FS ototoxicity promotes cochlear inflammation and SGN degeneration.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Canamicina
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Transdução de Sinais
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Fator de Crescimento Transformador beta
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Ototoxicidade
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article