Identification and experimental validation of ferroptosis-related gene lactotransferrin in age-related hearing loss.

Objective: To reveal the relationship between ARHL and ferroptosis and screen ferroptosis-related genes (FRGs) in ARHL.

Methods: Bioinformatics were used to analyze the hub genes and molecular mechanism of ferroptosis in the aging cochleae. Senescence β-galactosidase staining, iron content detection, and micro malondialdehyde (MDA) assay kits were used to measure β-galactosidase activity, and expression of Fe and MDA, respectively. Fluorescence microscope was used for immunofluorescence assay of hub genes. Western blot was used to verify the expression of hub genes in HEI-OC1 cells, cochlear explants, and cochleae of C57BL/6J mice. Data were expressed as mean ± SD of at least three independent experiments.

Results: The analysis of bioinformatics confirmed that lactotransferrin (LTF) is the hub gene and CEBPA-miR-130b-LTF network is the molecular mechanism for cochlear ferroptosis. Compared with the control group, the experiments proved that the indicators of ferroptosis, including Fe, MDA, and LTF were differentially expressed in aging HEI-OC1 cells, aging cochlear explants, and aging cochleae.

Conclusion: These results demonstrate that ferroptosis plays an important role in ARHL, and LTF is a potential therapeutic target for ARHL via regulating cochlear ferroptosis.