Abstract
BackgroundRecently, the role of several microRNAs (miRNAs or miRs) in pulmonary diseases has been described. The molecular mechanisms by which miR-214 is possibly implicated in bronchopulmonary dysplasia (BPD) have not yet been addressed. Hence, this study aimed to investigate a putative role of miR-214 in alveolarization among preterm neonates with BPD.MethodsMicroarray-based gene expression profiling data from BPD was employed to identify differentially expressed genes. A BPD neonatal rat model was induced by hyperoxia. Pulmonary epithelial cells were isolated from rats and exposed to hyperoxia to establish cell injury models. Gain- and loss-of-function experiments were performed in BPD neonatal rats and hyperoxic pulmonary epithelial cells. MiR-214 and PlGF expression in BPD neonatal rats, and eNOS, Bcl-2, c-myc, Survivin, α-SMA and E-cadherin expression in hyperoxic pulmonary epithelial cells were measured using RT-qPCR and Western blot analysis. The interaction between PlGF and miR-214 was identified using dual luciferase reporter gene and RIP assays. IL-1β, TNF-a, IL-6, ICAM-1 and Flt-1 expression in the rat models was measured using ELISA.ResultsThe lung tissues of neonatal rats with BPD showed decreased miR-214 expression with elevated PlGF expression. PlGF was found to be a target of miR-214, whereby miR-214 downregulated PlGF to inactivate the STAT3 pathway. miR-214 overexpression or PlGF silencing decreased the apoptosis of hyperoxic pulmonary epithelial cells in vitro and restored alveolarization in BPD neonatal rats.ConclusionOverall, the results demonstrated that miR-214 could facilitate alveolarization in preterm neonates with BPD by suppressing the PlGF-dependent STAT3 pathway.
Highlights
The role of several microRNAs in pulmonary diseases has been described
Results miR‐214 is predicted to orchestrate placental growth factor (PlGF) expression to mediate the signal transducer and activator of transcription 3 (STAT3) pathway in bronchopulmonary dysplasia (BPD) It has been reported that PlGF is an important gene participating in BPD in preterm infants, but the regulatory pathways of this gene are still unknown, representing an area of significant research potential (Janer et al 2008)
Our findings illustrated that miR-214 was downregulated in hyperoxia-induced BPD neonatal rats. miR-214, a miRNA precursor, plays a pivotal role in the pathogenesis of multiple human disorders, including cardiovascular (See figure on page.) Fig. 7 miR-214 overexpression blocks the effect of the activated STAT3 pathway on bronchial embryonic pulmonary epithelial cells by inhibiting PlGF
Summary
The role of several microRNAs (miRNAs or miRs) in pulmonary diseases has been described. This study aimed to investigate a putative role of miR-214 in alveolarization among pre‐ term neonates with BPD. PlGF has been found to increase under hyperoxic exposure, and downregulating PlGF can ameliorate hyperoxia-induced lung impairment in neonatal rats (Zhang et al 2020). Neonatal exposure to hyperoxia reportedly leads to a significant increase in STAT3 mRNA expression in pulmonary endothelial cells (Chao et al 2018). In this regard, we hypothesized that a regulatory network of the miR-214/PlGF/STAT3 pathway may be involved in BPD. The current study aimed to verify an involvement of the miR-214/PlGF/ STAT3 axis in BPD and elucidate its relevant molecular mechanisms
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call