MiRacles for babies with pulmonary hypoplasia: the effects of miR-10a and miR-200b on lung development
Loading...
Date
2015
Authors
Visser, Robin
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
INTRODUCTION: Pulmonary hypoplasia causes high morbidity and mortality in congenital diaphragmatic hernia (CDH) patients. MiR-10a and miR-200b are overexpressed in human CDH lungs. We aimed to define their roles in lung development. METHODS: We profiled miR-10a expression with RT-qPCR and in situ hybridization using a nitrofen rat model for CDH. The effects of miR-10a on airway branching were evaluated in lung explants. MiR-200b’s role in airway branching was assessed in miR-200b knockout lung explants. Crossing miR-200b knockout mice with CFP-E-Cadherin was used to evaluate miR-200b’s effects on epithelial differentiation. RESULTS: Expression of miR-10a was altered in the nitrofen model and miR-10a mimics reversed lung hypoplasia in vitro. Heterozygous miR-200b lung explants displayed reduced airway branching. CFP-E-Cadherin/miR-200b knockout lung explants showed reduced epithelial expression. CONCLUSION: Both miR-10a and miR-200b are critical for lung development and CDH. Normalizing their expression may reverse lung hypoplasia and reduce the associated morbidity and mortality in CDH.
Description
Keywords
congenital diaphragmatic hernia, lung development, miR-10a, miR-200b, pulmonary hypoplasia