GENE REGULATION OF AIRWAY CELL DIFFERENTIATION

这项提案的长期研究目标是了解分子 参与“粘液性”发展的机制 气道上皮的“分化”。 这些粘膜纤毛的功能 在肺部疾病和肺防御中的重要作用。 但 粘液纤毛调节的分子机制 差异尚未阐明。 的总体假设 建议是测试粘膜纤毛分化的表达是否 由多种维生素A反应基因调控。 为了解决这一假设，一个明确的维生素A依赖性粘液细胞， 人/猴气管支气管上皮细胞分化系统 细胞培养将用于阐明各种维生素A的作用， 应答基因，尤其是最早期的应答基因在调控中的作用。 具体而言，研究设计和目标是： 1)分离和表征参与 气道粘液细胞分化，以证实这一假设， mRNA水平上的基因表达与早期事件相关， 维生素A诱导的粘液细胞分化。 2)阐明了维生素A调节细胞凋亡的机制， 这些早期基因来检验基因表达变化的假设， 特别是在早期，发生在转录水平。 3)阐明这些早期维生素A反应基因在 调节维生素A诱导的粘液细胞分化，以支持 假设这些早期基因参与了粘液的起始， 维生素A诱导的细胞分化。

The long-term research goal of this proposal is to understand the molecular mechanisms that are involved in the development of "mucocillary differentiation" of airway epithelium. These mucociliary function play important roles in lung diseases and pulmonary defense. However, the molecular mechanism involved in the regulation of mucociliary differentiation has not been elucidated. The overall hypothesis of the proposal is to test if the expression of mucociliary differentiation is regulated by various vitamin A-responsive genes. To address this hypothesis, qa well-defined vitamin A-dependent mucous cell differentiation system of human/monkey tracheobronchial epithelial (TBE) cell culture will be used to elucidate the roles of various vitamin A- responsive genes, especially the earliest ones, in the regulation. Specifically, the research designs and aims are: 1) isolate and characterize early vitamin A-responsive genes involved in airway mucous cell differentiation to confirm the hypothesis that change in gene expression at the mRNA level is associated with the early event of vitamin A-induced mucous cell differentiation. 2) Elucidate the mechanism of vitamin A in regulating t he expression of these early genes to test the hypothesis that change in gene expression, especially at the early period, occurs at the transcriptional level. 3) Elucidate the roles of these early vitamin A-responsive genes in the regulation of vitamin A-induced mucous cell-differentiation to support the hypothesis that these early genes are involved in the initiation of mucous cell differentiation induced by vitamin A.