AUTHOR=Zeng Chaojun , Gu Xi , Chen Yuqing , Lin Yanchun , Chen Junying , Chen Zhifeng , Chen Chenyu , Yao Guangnan , Lin Chang 

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=16

YEAR=2024

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2024.1309115

DOI=10.3389/fnagi.2024.1309115

ISSN=1663-4365

ABSTRACT=<sec id="sec1"><title>Objective</title><p>To reveal the relationship between ARHL and ferroptosis and screen ferroptosis-related genes (FRGs) in ARHL.</p></sec><sec id="sec2"><title>Methods</title><p>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<sup>2+</sup> 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.</p></sec><sec id="sec3"><title>Results</title><p>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<sup>2+</sup>, MDA, and LTF were differentially expressed in aging HEI-OC1 cells, aging cochlear explants, and aging cochleae.</p></sec><sec id="sec4"><title>Conclusion</title><p>These results demonstrate that ferroptosis plays an important role in ARHL, and LTF is a potential therapeutic target for ARHL via regulating cochlear ferroptosis.</p></sec>