Role of MicroRNAs in Bronchopulmonary Dysplasia

描述（由申请人提供）：支气管肺发育不良（BPD）是一种慢性肺部疾病，发生在接受氧气和机械通气治疗的早产儿中。BPD导致肺部发育停滞。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利用非编码的~22核苷酸小RNA，即microRNAs (miRNAs)，它们与发育、细胞增殖和分化以及细胞凋亡有关。然而，关于mirna在发育性肺部疾病进展中的作用知之甚少。我们假设，在新生儿肺BPD的发展过程中，miRNAs被失调，这些miRNAs调节了BPD发展的基因。使用miRNA微阵列，Specific Aim 1将检测正常和BPD肺的miRNA谱。Specific Aim 2将确定所选mirna在BPD中的功能作用。mirna在肺中的功能的阐明将有助于了解肺发育的正常机制，并有助于设计BPD的治疗方法。项目描述：本提案的目的是确定与支气管肺发育不良（一种影响全球低体重早产儿的疾病）进展相关的microrna。microRNA在正常肺和病变肺中的功能的阐明将为支气管肺发育不良的发病机制提供见解，也将有助于该疾病的治疗干预的发展。

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.