LncRNA MIAT binding to GATA3 activates MAPK signaling pathway and influences bronchopulmonary dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) manifests in premature neonates with aberrant pulmonary function. Numerous long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of BPD. This study aims to elucidate the impact of the lncRNA myocardial infarction-associated transcript (MIAT) on the initiation and progression of BPD. Initially, BPD murine models were established through hyperoxia induction in newborn mice. Subsequently, MIAT and GATA binding protein 3 (GATA3) expression levels were assessed, and intravenous administration of short hairpin RNAs (shRNAs) targeting MIAT and GATA3 was performed. Pulmonary histological alterations were examined through histological staining. Levels of inflammatory mediators were quantified using enzyme-linked immunosorbent assay (ELISA) kits. The interaction between MIAT and GATA3 was scrutinized through RNA immunoprecipitation, RNA pull-down, and fluorescence in situ hybridization. The downstream mechanisms of GATA3 were explored using bioinformatics analysis. In summary, lncRNA MIAT exhibited elevated expression in the lung tissues of BPD-afflicted mice. MIAT localized to the nucleus and interacted with GATA3, thereby activating the mitogen-activated protein kinase (MAPK) pathway. Knockdown of MIAT or silencing of GATA3 attenuated the inflammatory response, deactivated the MAPK pathway, and ameliorated BPD symptoms in mice, on the other hand, p-Cresyl sulfate potassium can activate the MAPK signaling pathway and attenuates the effects of si-MIAT or si-GAT3. These improvements were characterized by enhanced alveolar differentiation and reduced glycogen and collagen deposition. In conclusion, lncRNA MIAT plays a pivotal role in activating the MAPK pathway and exacerbating hyperoxia-induced BPD in mice through the binding to GATA3. It's an important discovery for the pathogenesis of BPD and may provide some new treatment for infants diagnosed with BPD.