Butyrate silences <i>MUC5AC</i>expression in airway epithelial cells by mediating histone deacetylation at its transcription start site

Abstract Secreted airway mucins form a mucous gel consisting of MUC5AC and MUC5B maintain homeostasis for appropriate mucociliary clearance defense. There is conceivably global mechanism to counteract excessive mucin production in response incessant exposure external internal stimuli, which otherwise leads goblet metaplasia mucus hyperproduction. Here, we report that butyrate, short-chain fatty acid (SCFA), strongly suppresses at as low sub-to micromolar concentrations NCI-H292, epithelial cells. Butyrate transcriptionally inhibits mRNA protein are induced by variety stimuli including EGF LPS. In line, butyrate upregulates FOXA2, known block cell metaplasia. The mode the inhibition appears be independent receptors butyrate. addition, does not alter EGFR signaling pathway. Chromatin immunoprecipitation analysis demonstrates histone H3K27 acetylation level increased upon stimulation with returns baseline presence We propose metabolic product gut microbiota, plays central role maintaining counteracting resulting from repeated provocation epithelium. National Research Foundation Korea (NRF) funded Korean government (MSIT), NRF-2022R1A2B5B01002127.