Micro-RNAs in airway epithelial differentiation and asthma

描述（由申请人提供）：我们的长期目标是了解气道上皮细胞微rna （miRNAs）的功能，并确定这些miRNAs如何与哮喘有关。纤毛细胞和分泌细胞在气道上皮内建立并维持一个保护屏障。上皮细胞功能的改变是哮喘的一贯特征，并导致气道阻塞、发病率和死亡率。令人兴奋的最新进展表明，mirna调节许多基因的表达，并在发育和疾病中发挥重要作用。然而，mirna对气道上皮细胞分化和功能的贡献以及这些mirna在哮喘中的作用仍然未知。我们的初步数据表明，在气道上皮细胞分化过程中，miRNA的表达发生了显著变化，哮喘和健康受试者的miRNA表达存在显著差异。我们建议开发测量和操纵气道上皮细胞中miRNA水平和活性的方法。我们将使用这些方法来研究在初步研究中鉴定的精选mirna如何影响气道上皮细胞分化和基因表达。这些r21资助的研究结果将为后续的R01项目奠定基础，这些项目将探索基于mirna的哮喘治疗的潜力。

DESCRIPTION (provided by applicant): Our long-term objective is to understand how airway epithelial cell micro-RNAs (miRNAs) function and determine how these miRNAs contribute to asthma. Ciliated and secretory cells within the airway epithelium establish and maintain a protective barrier. Changes in epithelial cell function are a consistent feature of asthma and contribute to airway obstruction, morbidity, and mortality. Exciting recent advances demonstrate that miRNAs regulate expression of many genes and that miRNAs play major roles in development and disease. However, the contributions of miRNAs to airway epithelial cell differentiation and function and the roles of these miRNAs in asthma remain unknown. Our preliminary data demonstrate that miRNA expression changes dramatically during airway epithelial cell differentiation, and that there are significant differences in miRNA expression between asthmatic and healthy subjects. We propose to develop approaches for measuring and manipulating miRNA levels and activities in airway epithelial cells. We will use these approaches to study how selected miRNAs identified in the preliminary studies affect airway epithelial cell differentiation and gene expression. Results of these R21-funded studies will set the stage for subsequent R01 projects that will explore the potential of miRNA-based therapies for asthma. PUBLIC HEALTH RELEVANCE: Cells that line the airways are important in health and in diseases such as asthma. MicroRNAs are a recently identified class of important regulatory molecules but very little is known about their function in these cells. We will address this knowledge gap to identify new approaches for diagnosing and treating airway diseases.