Journal: Nature Communications
Article Title: Supporting cells orchestrate noise-induced hearing loss via a Gasdermin D-dependent signaling loop with hair cells
doi: 10.1038/s41467-025-66152-6
Figure Lengend Snippet: a Comparison of GSDMD changes between WT and Tlr4 KO mice following noise exposure, evaluated at 8 h-PNE. Detection parameters included short exposure (5 s) and prolonged exposure (30 s) to visualize GSDMD-FL and GSDMD-N bands, respectively. b , c Effect of Zorifertinib (EGFR inhibitor) on GSDMD, 4HNE, p-ERK, and t-ERK levels in WT mice after NE, evaluated at 8 h-PNE. d Representative confocal and 3D images of p-ERK (green) in cochlear tissues before and immediately after noise exposure. e – g Effect of Dabrafenib (an inhibitor to reduce p-ERK levels) on GSDMD, 4HNE, p-ERK, and t-ERK levels in WT mice after NE, evaluated at 8 h-PNE. h Representative WB analysis of p-ERK and t-ERK in cochlea transfected with/without AAV-HC- Gpx4 . The p-ERK/t-ERK ratios were normalized to β-actin as a loading control and presented as fold-changes relative to the vehicle group (set to 1). i Immunolabeling of p-ERK (green) in the 22.6–32 kHz cochlear region in non-AAV and AAV-HC- Gpx4 -transfected mice with noise exposure, observed at 0 h-PNE. A significant reduction in p-ERK activation was observed in the OHC region of Gpx4 -transfected mice. All data are presented as mean ± SEM ( n = 3 biological replicates). Statistical analysis was performed using one-way ANOVA with Bonferroni post hoc test. ns, not significant. Scale bar = 10 μm. WT wild type, NE noise exposure, Zori Zorifertinib, Dab Dabrafenib, SCs supporting cells, OHC outer hair cells, IHC inner hair cells, PC pillar cells, DC Deiter cells, p-ERK phosphorylated ERK, t-ERK total ERK.
Article Snippet: Zorifertinib (HY-18750), Dabrafenib mesylate (HY-14660) and ASN007 (HY-136579A) were purchased from MedChemExpress.
Techniques: Comparison, Transfection, Control, Immunolabeling, Activation Assay