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

Abstract

Background: 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 . 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. Methods: 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. Results: 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. Conclusion: 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.

Chitin-Derived AVR-48 Prevents Experimental Bronchopulmonary Dysplasia (BPD) and BPD-Associated Pulmonary Hypertension in Newborn Mice

“…In agreement with published literature and prior studies [32][33][34], there was a significant increase in neutrophils [35] and dendritic cells [36] in the BPD group over the RA group (Supplemental Figure S7C). Interestingly, AVR-48 treated BPD animals had decreased neutrophils and increased macrophages compared to untreated BPD animals, and these cell populations were at similar levels as the RA control group.…”

Selecting Hub Genes and Predicting Target Genes of microRNAs in Tuberculosis via the Bioinformatics Analysis

“…The hsa-mir-7 was thought to be involved in innate immune responses in a previous study [ 31 ]. Meanwhile, hsa-mir-451 protects against cell death caused by ischemia/reperfusion injury, cancer, and myocardial I/R injury [ 32 – 34 ]. CAMP, CEACAM8, CD59, CLEC5A, STOM, MS4A3, GPR84, LAMTOR3, CEACAM1, and DEFA4 are among the ten hub genes discovered.…”

Recent advances in understanding and management of bronchopulmonary dysplasia

“…Pharmacologic inhibition of miR-34a can thus be used as a potential therapeutic option in neonates to prevent hyperoxia-induced lung injury 45 . In another study, increased expression of miR-451 was noted in animal models of BPD and inhibition of miR-451 was shown to improve the cardiopulmonary phenotype 46 . Similarly, potential roles for miR-17∼92 47 , miR-29b 48 , miR-876-3p 49 , miR-199a-5p 50 , and miR-489 51 have been described in the pathogenesis of BPD.…”