Supporting cells orchestrate noise-induced hearing loss via a Gasdermin D-dependent signaling loop with hair cells
Brief intro:
- Author: Lili Xiao, Jianju Liu, Yi Chen, Liang Xia, Yumeng Jiang, Xiaoyan Chen, Tianjiao Zhou, Yan Sun, Wen Lu, Hui Wang, Jian Wang, Yanmei Feng, Zhen Zhang, Shankai Yin
- Journal: Nature Communications
- Doi: https://www.doi.org/10.1038/s41467-025-66152-6
- Publication Date: 2025/12/17
Abstract
Noise-induced hearing loss (NIHL), a common sensory disorder, is traditionally thought to stem primarily from direct damage to sound-sensing hair cells (HCs). Here, we demonstrate that supporting cells (SCs), neighboring cells not previously implicated in NIHL pathogenesis, orchestrate hearing loss and HC degeneration through Gasdermin D (GSDMD) activation. Mechanistically, noise-induced oxidative stress in HCs triggers activation of epidermal growth factor receptor in SCs, leading to extracellular-regulated kinase phosphorylation and caspase-11-dependent cleavage of GSDMD, thereby establishing an HC-to-SC signaling cascade. Furthermore, GSDMD activation in SCs reciprocally exacerbates oxidative injury in HCs, creating a pathogenic positive feedback loop between the two cell types. Our findings uncover a central role for SCs in noise-induced hearing loss and identify GSDMD-mediated intercellular communication as a potential therapeutic target.
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