Transcriptomics Implicates the G3BP1-SG Axis in Cochlear Hair-Cell Pyroptosis During Age-Related Hearing Loss

Age-related hearing loss (ARHL) is a degenerative change in the auditory system, but its underlying mechanism remains unclear. In this study, using RNA sequencing technology, we analysed the expression profiles of mRNAs in the cochlear tissues of ARHL-susceptible C57BL/6J (C57) mice and relatively resistant CBA/CaJ (CBA) mice. We found that the mRNA related to stress granules (SGs) was significantly increased in the cochlear tissues of ARHL mice. Combined with current research on the pyroptosis of cochlear hair cells, we constructed an aging model of House Ear Institute-Organ of Corti 1 (HEI-OC1) in vitro and found that the expression of SG was upregulated and the expression of pyroptosis-related proteins showed a synergistic upregulation. Furthermore, functional studies involving both G3BP1 knockdown and overexpression suggested that stress granules exert a protective effect by negatively regulating pyroptosis in HEI-OC1 cells. In summary, the results of this study indicate that with aging, the formation of SG increases and the activation of pyroptosis-related markers is enhanced. The dysfunction of G3BP1 further exacerbates these pyroptosis markers, supporting the protective role of SG homeostasis in inhibiting pyroptosis activation under stress conditions. Preliminary verification suggests that the SG-pyroptosis axis may be a potential target for regulating the pyroptosis of cochlear hair cells.