The Role and Mechanism of GSDME-Dependent Pyroptosis in Cochlear Marginal Cells Injury by Cisplatin
<b>Background:</b> Elucidating the mechanisms underlying cisplatin-induced ototoxicity is critical for the clinical management of hearing loss. While cisplatin is known to penetrate the inner ear via the blood-labyrinth barrier in the stria vascularis, its precise damaging effects on mar...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-07-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/7/1680 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | <b>Background:</b> Elucidating the mechanisms underlying cisplatin-induced ototoxicity is critical for the clinical management of hearing loss. While cisplatin is known to penetrate the inner ear via the blood-labyrinth barrier in the stria vascularis, its precise damaging effects on marginal cells (MCs) and subsequent hearing impairment remain incompletely understood. Pyroptosis, a gasdermin-mediated inflammatory cell death pathway, may play a key role. This study investigated the involvement of gasdermin E (GSDME)-dependent pyroptosis in cisplatin-induced injury to MCs. <b>Methods:</b> An in vitro cisplatin-induced pyroptosis model was established in MCs. GSDME expression was downregulated using small interfering RNA (siRNA), and caspase-3 activity was inhibited pharmacologically. The critical threshold for pyroptosis induction was determined to be 5 μmol/L cisplatin exposure for 24 h, which activated the caspase-3/GSDME signaling pathway. <b>Results:</b> Cisplatin treatment upregulated GSDME and caspase-3 expression in MCs. Both inhibition of GSDME and pharmacological blockade of caspase-3 significantly attenuated cisplatin-induced cellular damage. Notably, caspase-3 suppression reduced GSDME expression, suggesting a positive regulatory relationship between these mediators. <b>Conclusions:</b> GSDME-mediated pyroptosis plays a pivotal role in cisplatin-induced marginal cell injury, with caspase-3 acting as an upstream regulator of GSDME expression. These findings provide a mechanistic foundation for developing novel therapeutic strategies against cisplatin ototoxicity. |
|---|---|
| ISSN: | 2227-9059 |