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Inhibition of microRNA-451 is associated with increased expression of Macrophage Migration Inhibitory Factor and mitgation of the cardio-pulmonary phenotype in a murine model of Bronchopulmonary Dysplasia
Journal article   Open access   Peer reviewed

Inhibition of microRNA-451 is associated with increased expression of Macrophage Migration Inhibitory Factor and mitgation of the cardio-pulmonary phenotype in a murine model of Bronchopulmonary Dysplasia

Margaret Gilfillan, Pragnya Das, Dilip Shah, Mohammad Afaque Alam and Vineet Bhandari
Respiratory research, v 21(1), pp 92-92
22 Apr 2020
DOI: https://doi.org/10.1186/s12931-020-01353-9
PMID: 32321512
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1186/s12931-020-01353-9View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Animals Animals, Newborn Bronchopulmonary Dysplasia - genetics Bronchopulmonary Dysplasia - metabolism Bronchopulmonary Dysplasia - pathology Cells, Cultured Disease Models, Animal Gene Expression Intramolecular Oxidoreductases - biosynthesis Intramolecular Oxidoreductases - genetics Macrophage Migration-Inhibitory Factors - biosynthesis Macrophage Migration-Inhibitory Factors - genetics Mice MicroRNAs - antagonists & inhibitors MicroRNAs - biosynthesis MicroRNAs - genetics Oligonucleotides - pharmacology Phenotype Random Allocation
Macrophage migration inhibitory factor (MIF) has been implicated as a protective factor in the development of bronchopulmonary dysplasia (BPD) and is known to be regulated by MicroRNA-451 (miR-451). The aim of this study was to evaluate the role of miR-451 and the MIF signaling pathway in in vitro and in vivo models of BPD. Studies were conducted in mouse lung endothelial cells (MLECs) exposed to hyperoxia and in a newborn mouse model of hyperoxia-induced BPD. Lung and cardiac morphometry as well as vascular markers were evaluated. Increased expression of miR-451 was noted in MLECs exposed to hyperoxia and in lungs of BPD mice. Administration of a miR-451 inhibitor to MLECs exposed to hyperoxia was associated with increased expression of MIF and decreased expression of angiopoietin (Ang) 2. Treatment with the miR-451 inhibitor was associated with improved lung morphometry indices, significant reduction in right ventricular hypertrophy, decreased mean arterial wall thickness and improvement in vascular density in BPD mice. Western blot analysis demonstrated preservation of MIF expression in BPD animals treated with a miR-451 inhibitor and increased expression of vascular endothelial growth factor-A (VEGF-A), Ang1, Ang2 and the Ang receptor, Tie2. We demonstrated that inhibition of miR-451 is associated with mitigation of the cardio-pulmonary phenotype, preservation of MIF expression and increased expression of several vascular growth factors.

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24 citations in Web of Science
30 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Respiratory System
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