LncRNA XIST, as a ceRNA of miR-204, aggravates lipopolysaccharide-induced acute respiratory distress syndrome in mice by upregulating IRF2

Acute respiratory distress syndrome (ARDS) is a common clinical syndrome with high a mortality rate, which is associated with diffuse alveolar injury and capillary endothelial damage. In recent years, numerous studies have been performed to explore the roles of long non-coding RNAs (lncRNAs) in various diseases in which lncRNA serves as a microRNA (miRNA) sponge to regulate targeted gene expression. However, whether lncRNAs participate in ARDS progression remains unclear. The dual-luciferase reporter assay was employed to identify the interaction between lncRNA XIST and miR-204, as well as the correlation between miR-204 and interferon regulatory factor 2 (IRF2). Then, PaO /FiO was determined in lipopolysaccharide (LPS)-induced ARDS. In addition, the concentrations of cytokines, including IFN-γ, IL-6, IL-17, TNF-α, IL-1β, and IL-6R were analyzed by ELISA. lncRNA XIST, miR-204, and IRF2 levels were determined by qRT-PCR assay, and the IRF2 expression was evaluated by western blot. Furthermore, levels of inflammation and conditions of alveoli were evaluated by hematoxylin (H&E)-staining in LPS-induced ARDS. Our findings indicated that lncRNA XIST served as a sponge for miR-204. miR-204 directly regulated IRF2, andlncRNA XIST upregulated IRF2 expression by targeting miR-204. LncRNA XIST and miR-204 inhibitors significantly decreased the PaO /FiO ratio, whereas miR-204 and silencing of IRF2 significantly increased the PaO /FiO ratio in LPS-induced ARDS. In addition, lncRNA XIST and miR-204 inhibitors significantly increased levels of IFN-γ, IL-6, IL-17, TNF-α, IL-1β, and IL-6R, whereas miR-204 and silencing of IRF2 dramatically decreased related cytokines in LPS-induced ARDS. Furthermore, we demonstrated that lncRNA XIST and miR-204 inhibitors aggravated inflammatory cell infiltration, alveolitis, and the degree of fibrosis, whereas miR-204 and silencing of IRF2 alleviated inflammation and conditions of the alveoli. In this study, we verified that lncRNA XIST serves as a sponge for miR-204 to aggravate LPS-induced ARDS in mice by upregulating IRF2.