Congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia and pulmonary hypertension (PH) leading to a high morbidity and mortality. MicroRNAs, affect gene expression and miR-200b is involved in epithelial-mesenchymal transition in cancer and is downregulated in rat nitrofen lungs.
We hypothesised that miR-200b regulates lung branching. Therefore, we aimed to evaluate whether in vivo administration of miR-200b influences lung development and branching morphogenesis.
Timed-pregnant dams were treated with nitrofen (CDH group) or olive oil (control group) on E9 and received a tail vein injection of miR-200b mimics (5 mg/kg) or saline, respectively. At E21.5 and P0, we dissected the lungs and evaluated the presence or absence of CDH. We estimated the lung hypoplasia and we did histological studies to determine radial alveolar count (RAC) and medial arterial thickness.
Nitrofen lungs treated with miR-200 b mimics, in vivo display improved development and larger size. These embryos were also bigger than the embryos of the nitrofen group plus saline. Their size was similar to control embryos. After RAC analysis revealed that nitrofen treated lungs have larger alveolar spaces than nitrofen lungs. In terms of arteries we did not observe any differences.
Administration of miR-200b in vivo decreases lung hypoplasia and increases the size of the lungs as well as alveolar airspaces. These data show promissing results for miR-200b as a potential therapeutic target in CDH patients.
- This work was supported by grants from the MICH, MMSF, Molly Towell, GFT surgeons and Thorlakson Foundation.