Role of MicroRNAs in Bronchopulmonary Dysplasia

描述(申请人提供)：支气管肺发育不良(BPD)是一种慢性肺部疾病，发展为早产儿的氧气和机械通气治疗。BPD会导致肺部发育受阻。BPD的发病机制尚不完全清楚。在器官发生过程中，一种新的基因调控途径是利用非编码的~22个核苷酸的小RNA，microRNAs(MiRNAs)，它与发育、细胞增殖和分化以及细胞凋亡有关。然而，关于miRNAs在发育性肺部疾病进展中的作用，人们知之甚少。我们假设miRNAs在BPD的发展过程中在新生儿肺中处于失调状态，并且这些miRNAs调控与BPD发生相关的基因。利用miRNA微阵列，特殊目标1将检查正常和BPD肺的miRNA图谱。具体目标2将确定选定的miRNAs在BPD中的功能作用。阐明miRNAs在肺中的功能将有助于深入了解肺发育的正常机制，并有助于设计治疗BPD的方法。项目简介：这项建议的目的是确定与支气管肺发育不良进展相关的MicroRNAs，这是一种在全球范围内影响低体重早产儿的疾病。阐明正常肺和病变肺中microRNA的功能将有助于深入了解支气管肺发育不良的发病机制，也将有助于开发对该疾病的治疗干预措施。

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.