ABSTRACT To investigate the mechanism by which BRD4 accelerates acute lung injury (ALI) by promoting ferroptosis mediated by ANP32B/H3K27ac/MYC/HOXB8/BACH1 in alveolar epithelial cells. Gene co‐expression was analyzed with bioinformatics. Eighteen SPF‐grade C57BL/6J male mice (6–8 weeks old, 20 ± 4 g) were divided into three groups: Sham, Model, and Model‐JQ1. Lung function was analyzed post‐anesthesia; after euthanasia, lung tissues were collected for TEM to observe structural changes. HE staining assessed cellular morphology and pathology, while Prussian blue staining evaluated iron deposition. Western Blot detected BRD4, ANP32B, MYC, HOXB8, and BACH1 protein expression. ELISA measured GSH, MDA, lipid ROS, Fe 2+ , and LPO levels. MLE‐12 cells were cultured and divided into four groups: NC, LPS, LPS‐JQ1, and LPS‐JQ1‐BACH1‐OE. Western Blot and immunofluorescence analyzed protein expression, and TEM observed cell ultrastructure. ELISA assessed oxidative stress markers. HOXB8 regulates BACH1, impacting oxidative stress and iron metabolism genes. LPS induced significant cell damage, alleviated by BRD4 inhibition. JQ1 improved lung injury and function, reduced iron accumulation, and oxidative damage. Western Blot and ELISA showed LPS upregulated key proteins, reversed by BRD4 inhibition. JQ1 inhibited LPS‐induced stress in cells; BACH1 overexpression partially reversed this. Immunofluorescence showed BRD4 inhibition suppressed BACH1 and promoted SLC7A11 expression. ALI is accelerated by BRD4 through the promotion of ANP32B/H3K27ac/MYC/HOXB8/BACH1‐mediated ferroptosis in alveolar epithelial cells. A deeper understanding of the role of BRD4 in alveolar epithelial cell injury is provided by these findings, and potential therapeutic targets for the treatment of ALI may be identified.
Liu et al. (Fri,) studied this question.