The role of microRNA-200b in pulmonary hypoplasia associated with congenital diaphragmatic hernia

Abstract

Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that is associated with pulmonary hypoplasia. MicroRNAs are small RNAs that regulate protein expression. In this project the role of micro-RNA 200b (miR-200b) in CDH was explored through in situ hybridization. In human tissue, CDH was associated with increased miR-200b expression. In rats, nitrofen-induced CDH was associated with decreased miR-200b expression. In mesenchymal tissue, miR-200b expression was high in undifferentiated splanchnic mesenchyme. Its expression dropped with increasing gestational age and in proximal parabronchial smooth muscle cells. In epithelium, miR-200b expression was highest at the elongating tips of the bronchial tree. Using immunohistochemistry, expression of vimentin was demonstrated in the distal epithelium during branching morphogenesis. Theses results indicate that lung branching morphogenesis occurs through epithelial-to-mesenchymal transition of the distal epithelium and miR-200b functions in epithelial differentiation. Abnormal miR-200b expression accounts for differences in epithelial differentiation between human and nitrofen-induced CDH.