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Published on: May 4, 2020
MicroRNA-214 promotes alveolarization in neonatal rat models of bronchopulmonary dysplasia via the PlGF-dependent
Zhi-Qun Zhang1, Hui Hong2, Jing Li2
1Department of Neonatology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No. 261, Huansha Road, Hangzhou, 310000, Zhejiang Province, People's Republic of China. zhiqun.zhang@zju.edu.cn.
Background:
Recently, 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.
Methods:
Microarray-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.
Results:
The 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.
Conclusion:
Overall, the results demonstrated that miR-214 could facilitate alveolarization in preterm neonates with BPD by suppressing the PlGF-dependent STAT3 pathway.
Insights
MicroRNA-214 (miR-214) plays a crucial role in preventing bronchopulmonary dysplasia (BPD) by downregulating placental growth factor (PlGF). This finding offers a potential therapeutic target for improving alveolarization in preterm infants.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Neonatology
Background:
- Bronchopulmonary dysplasia (BPD) is a chronic lung disease affecting preterm infants.
- The molecular mechanisms underlying BPD, particularly the role of microRNAs, remain incompletely understood.
- MicroRNA-214 (miR-214) has emerged as a potential factor in pulmonary disease, but its specific role in BPD is uninvestigated.
Purpose of the Study:
- To investigate the role of miR-214 in alveolarization in preterm neonates with BPD.
- To elucidate the molecular mechanisms by which miR-214 may influence BPD pathogenesis.
- To explore miR-214 as a potential therapeutic target for BPD.
Main Methods:
- Gene expression profiling and a hyperoxia-induced rat model of BPD were used.
- Gain- and loss-of-function experiments were conducted in vivo and in vitro.
- Expression levels of miR-214, PlGF, and related signaling pathway molecules were quantified using RT-qPCR, Western blot, and ELISA.
Main Results:
- Neonatal rat lungs with BPD exhibited decreased miR-214 and increased placental growth factor (PlGF) expression.
- miR-214 directly targets and downregulates PlGF, thereby inactivating the STAT3 pathway.
- Overexpression of miR-214 or silencing of PlGF reduced apoptosis and improved alveolarization in BPD models.
Conclusions:
- miR-214 facilitates alveolarization in BPD by suppressing the PlGF-dependent STAT3 pathway.
- These findings highlight miR-214 as a key regulator in BPD development.
- Targeting the miR-214/PlGF axis presents a promising therapeutic strategy for BPD.
