methyltransferase-like 3 (mettl3) epigenetically modulates glutathione peroxidase 4 (gpx4) expression to affect asthma

Asthma, a prevalent chronic airway inflammatory condition, poses a significant health challenge. in this study, we delved into the regulatory mechanisms governing asthma, focusing on methyltransferase-like 3 (mettl3).through an ovalbumin (ova)-induced mouse model and interleukin-13 (il-13)-induced cell model, we mimicked the in vivo and in vitro functions of mettl3 in asthma.our research revealed that mettl3 expression significantly decreased in asthma-induced mice and il-13-stimulated cells compared to the control group. moreover, mettl3 overexpression enhanced bronchial epithelial cell viability and proliferation. mechanistically, we observed elevated levels of total iron, fe2+, malondialdehyde (mda), lipid reactive oxygen species (ros), alongside reduced glutathione (gsh) levels in il-13-stimulated cells. remarkably, mettl3 overexpression counteracted these effects, suggesting a pivotal role in mitigating asthma-related oxidative stress. furthermore, our study highlighted the involvement of n6-methyladenosine methylation (m6a) modification, where mettl3 regulated the m6a modification of glutathione peroxidase 4 (gpx4) rna, impacting rna stability. knockdown of mettl3 suppressed m6a modification on gpx4 rna, impairing its stability and contributing to il-13-induced ferroptosis. interestingly, mettl3 overexpression not only inhibited cell ferroptosis but also alleviated asthma symptoms.our findings shed light on the epigenetic regulation of asthma through mettl3-mediated m6a modification, offering potential therapeutic avenues for this prevalent inflammatory disease.