Role of MicroRNAs in Bronchopulmonary Dysplasia

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DESCRIPTION (provided by applicant): Bronchopulmonary dysplasia (BPD) is a chronic lung disease that develops in preterm neonates treated with oxygen and mechanical ventilation. BPD causes arrested lung development. The pathogenesis of BPD is still not completely understood. A novel pathway for gene regulation during organogenesis utilizes non-coding ~22-nucleotide small RNA, microRNAs (miRNAs), which have been implicated in development, cell proliferation and differentiation, and apoptosis. However, very little is known regarding the role of miRNAs in the progression of developmental lung diseases. We hypothesize that miRNAs are dysregulated during the progression of BPD in neonatal lungs and that these miRNAs regulate genes responsible for the development of BPD. Using miRNA microaroarray, Specific Aim 1 will examine miRNA profiles of the normal and BPD lungs. Specific Aim 2 will establish functional roles of the selected miRNAs in BPD. The elucidation of miRNAs' functions in the lung will provide insight into the normal mechanisms of lung development as well as aid in the design of therapies for BPD. Project Narrative: The purpose of this proposal is to identify the microRNAs that are associated with the progression of bronchopulmonary dysplasia, a disease that affects low- weight preterm infants worldwide. The elucidation of microRNA functions in normal lungs versus diseased lungs will provide insight as to the pathogenesis of bronchopulmonary dysplasia and will also aid in the development of therapeutic intervention for the disease.