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bioRxiv · 10.1101/2020.03.02.971572

MicroRNA-214 prevents pulmonary angiogenesis and alveolarization in rat models with hyperoxia-mediated impairment of lung development by blocking PlGF-dependent STAT3 signaling pathway

Zhang, Z.·Li, X.·Li, J.·Hong, H.·Huang, X.
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Abstract

In recent years, the roles of microRNAs (miRNAs) in pulmonary diseases have been widely studied and researched. However, the molecular mechanism by which miR-214 affects bronchopulmonary dysplasia (BPD) remains elusive and merits further exploration. Hence, this study aims to clarify the function of miR-214 in pulmonary angiogenesis and alveolarization in preterm infants with BPD. BPD neonatal rat model was induced by hyperoxia, and pulmonary epithelial cells were isolated from rats and exposed to hyperoxia. Gain- or 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, -SMA and E-cadherin expression in hyperoxic pulmonary epithelial cells were detected using RT-qPCR and western blot analysis. The interaction between PlGF and miR-214 was identified using dual luciferase reporter gene assay and RIP assay. ELISA was adopted to assess IL-1{beta}, TNF-a, IL-6, ICAM-1 and Flt-1 expression in rats. Decreased miR-214 expression and elevated PlGF expression were evident in the lung tissues of neonatal rats with BPD. PlGF was a target of miR-214, and miR-214 downregulated PlGF to inactivate the STAT3 signaling pathway. miR-214 overexpression or PlGF silencing decreased apoptosis of hyperoxic pulmonary epithelial cells and declined pulmonary angiogenesis and alveolarization in BPD neonatal rats. Collectively, miR-214 can protects against pulmonary angiogenesis and alveolarization in preterm infants with BPD by suppressing PlGF and blocking STAT3 signaling pathway.

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Zhang, Z., Li, X., Li, J., Hong, H., Huang, X.. 2020-03-03. MicroRNA-214 prevents pulmonary angiogenesis and alveolarization in rat models with hyperoxia-mediated impairment of lung development by blocking PlGF-dependent STAT3 signaling pathway. https://doi.org/10.1101/2020.03.02.971572

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