AUTHOR=Liang Mulin , Song Feifei , Wang Jin , Yang Chunli , Yin Huixi , Zhou Wei 

TITLE=Hydrogen regulates the aryl hydrocarbon receptor, improving bronchopulmonary dysplasia in neonatal rats and RLE-6TN cells exposed to hyperoxia

JOURNAL=Frontiers in Pediatrics

VOLUME=Volume 13 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2025.1662922

DOI=10.3389/fped.2025.1662922

ISSN=2296-2360

ABSTRACT=IntroductionThis study investigates the role and underlying mechanism of hydrogen (H₂) in hyperoxia-induced bronchopulmonary dysplasia (BPD), aiming to provide a theoretical foundation for developing effective BPD treatment strategies.MethodsA hyperoxia-induced BPD rat model and a rat type II alveolar epithelial cell (RLE-6TN) injury model were established. H₂ was administered to assess its effects on BPD rats, while hydrogen-rich medium was used to treat RLE-6TN cells to evaluate cell viability. In vivo and in vitro experiments were conducted to explore the regulatory influence of H₂ on the aryl hydrocarbon receptor (AHR). Additionally, AHR knockdown and overexpression experiments were performed to determine the impact of AHR on cell viability.ResultsH₂ treatment ameliorated lung tissue pathology in BPD rats, reduced cellular apoptosis, enhanced the expression of surfactant proteins SP-A and SP-B, and modulated AHR and its downstream effector CPEB4, thereby alleviating endoplasmic reticulum (ER) stress. IN vitro, hydrogen-rich medium mitigated RLE-6TN cell injury, promoted AHR nuclear translocation, and activated CPEB4 expression. AHR overexpression enhanced RLE-6TN cell viability and exhibited strong binding affinity to the CPEB4 promoter.DiscussionH₂ alleviates ER stress and reduces apoptosis by regulating AHR and its downstream molecule CPEB4, thereby mitigating hyperoxia-induced BPD. The protective mechanism of H₂ may be closely associated with the modulation of the AHR–CPEB4 signaling pathway and the attenuation of ER stress.