Mechanism of lncRNA H19 in Regulating Pulmonary Injury in Hyperoxia-Induced Bronchopulmonary Dysplasia Newborn Mice

Abstract

Objective Bronchopulmonary dysplasia (BPD) is a pulmonary injury related to inflammation and is a major cause of premature infant death. Long noncoding RNAs (lncRNAs) are important regulators in pulmonary injury and inflammation. We investigated the molecular mechanism of lncRNA H19 in pulmonary injury and inflammation in hyperoxia (Hyp)-induced BPD mice. Study Design The BPD newborn mouse model was established and intervened with H19 to evaluate the pathologic conditions and radial alveolar count (RAC) in lung tissues of mice in the room air (RA) and Hyp group on the 4th, 7th, and 14th days after birth. The levels of BPD-related biomarkers vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGF-β1), and surfactant protein C (SPC) in lung tissues were detected on the 14th day after birth. The expression of and relationships among H19 and miR-17, miR-17, and STAT3 were detected and verified. Levels of interleukin (IL)-6, IL-1β, p-STAT3, and STAT3 levels in mouse lung tissues were detected on the 14th day after birth. Results Hyp-induced mice showed increased alveolar diameter, septum, and hyperemia and inflammatory cell infiltration, upregulated H19, decreased overall number and significantly reduced RAC on the 7th and 14th days after birth, which were reversed in the si-H19-treated mice. VEGF was upregulated and TGF-β1 and SPC was decreased in si-H19-treated mice. Moreover, H19 competitively bound to miR-17 to upregulate STAT3. IL-6 and IL-1β expressions and p-STAT3 and STAT3 levels were downregulated after inhibition of H19. Conclusion Downregulated lncRNA H19 relieved pulmonary injury via targeting miR-17 to downregulate STAT3 and reduced inflammatory response caused by p-STAT3 in BPD newborn mice. Key Points

LncRNA gadd7 promotes mitochondrial membrane potential decrease and apoptosis of alveolar type II epithelial cells in hyperoxia-induced lung injury by promoting MFN1

“…LncRNAs, including lncRNA NEF, lncRNA CASC2, and lncRNA H19, are reported to have prominent roles in HALI. 18-20 Our results manifested that the lncRNA gadd7 expression and MFN1 levels were augmented after hyperoxia treatment, consistent with the already reported results. 16 , 17 Hyperoxia induces cell apoptosis and mitochondrial dysfunction in HALI.…”

“…Long non-coding RNAs (LncRNAs) are noncoding RNAs with more than 200 nucleotides, which are vital regulators in various biological processes. 18 LncRNA NEF modulates the lung epithelial cells in HALI through FOXA2. 19 LncRNA CASC2 targets CAV1 by competitively binding to miRNA-194-5p to suppress neonatal lung injury.…”

Recruitment of PVT1 Enhances YTHDC1-Mediated m6A Modification of IL-33 in Hyperoxia-Induced Lung Injury During Bronchopulmonary Dysplasia

“…Previous studies have highlighted the crucial roles of lncRNAs in the progression and treatment of BPD [ 38 – 41 ]. In this study, we have made an innovative discovery by demonstrating the significant upregulation of PVT1 in hyperoxia-stimulated lung alveolar epithelial cells through PCR analysis.…”