Bronchopulmonary dysplasia (BPD) is a chronic lung disease, which often occurs in preterm infants due to neonatal lung injury, and is defined by a lack of alveoli formation. Depending on the severity of the disease there are severe long-term consequences, such as early onset of chronic obstructive lung disease (COPD). Although a lot of progress has been made to improve the outcome of the disease, a cure has yet to be found. Therefore, it is imperative to investigate the development of BPD in order to identify new targets to improve the prognosis of the disease. In an experimental mouse model of hyperoxia induced BPD, a microarray showed an upregulation of microRNA (miR)-34a. It was also revealed, that miR-34a targets the platelet-derived growth factor receptors (PDGFR) alpha and beta, which are known to be crucial for fibroblast migration during secondary septation. Downstream signalling molecules of PDGFR alpha and beta are for example extracellular signal-regulated kinase (ERK) and AKT, also known as Protein Kinase B. In this thesis, a series of in vitro experiments including real-time quantitative polymerase chain reaction (qPCR), transfection, western blot analysis and migration assay, was conducted in mouse lung (MLg) fibroblasts, to investigate the effect of miR-34a on PDGFR alpha and beta and on fibroblast migration. It was revealed by qPCR analysis that hyperoxia firstly increases the level of the miR-34 family, most notably of miR-34a, and secondly reduces the expression of PDGFR alpha and beta in MLg fibroblasts. Transfecting MLg fibroblasts with miR-34a also showed a reduction of PDGFR alpha and beta levels. To further examine the effects of miR-34a on PDGFR alpha and beta, its downstream signalling molecules were investigated. Western blot analysis showed a reduced activation of downstream signalling, especially when stimulating the miR-34a transfected MLg fibroblasts with PDGFA, the specific ligand to PDGFR alpha. Furthermore, migration assays revealed reduced migration in MLg fibroblasts after miR-34a transfection, with and without stimulation of PDGFR alpha and beta with their ligands. In conclusion, these results suggest an important role of miR-34a as a negative regulator of fibroblasts migration via the PDGFR, and thus as a crucial factor in one of the mechanisms causing BPD. Therefore, further investigation of miR-34a and PDGFR interaction could contribute to a deeper understanding of BPD and ultimately improve the outcome of the disease.
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