MUCOUS CELL DIFFERENTIATION IN AIRWAY EPITHELIUM

粘膜纤毛功能是抵抗各种疾病的第一防御机制。 吸入污染物在传导气道上皮中的分布。 维生素A是一种 参与这些功能调节的最重要因素。 已经进行了许多研究，但维生素A调节的性质 在这些不同的功能仍然很不清楚。 外贸 该补助金（RO 1-HL 35635）支持表明， 来自人、猴和仓鼠气管支气管组织的细胞能够 在培养物中表达粘液细胞分化， 依赖于维生素A的存在。没有维生素A，上皮细胞 在培养物中表达鳞状细胞分化。 这次竞争性的续约 本申请涉及粘液细胞分化的生物学。 基于显微注射和基因克隆的初步研究， 我们假设维生素A调节两种粘液细胞的分化， 不同的阶段 第一阶段是主管阶段， 上皮细胞不定向为鳞状或粘液细胞 维生素A治疗后的分化。 第二阶段是关于 作为一个渐进的阶段，其中未定型的细胞致力于粘液 维生素A治疗后的细胞分化。 我们还假设 每个阶段都涉及不同的新基因表达。 是 建议研究这两个阶段的基因表达， 确定这些新基因在粘液细胞调节中的作用， 分化 我们的具体目标是：1）克隆和表征 维生素A反应基因，重点是那些参与早期 事件和分化，2）定义水平（即转录， 翻译）的基因表达调节维生素A，3），以确定 这些基因是否是粘液细胞 4）确定上皮细胞与粘液细胞的关系， 在双相器官型培养中的细胞类型特异性基因表达 系统 已经分离了几个维生素A应答cDNA克隆， 它们最初将用于定义粘液细胞的阶段 分化和阐明维生素A的调节机制。

Mucociliary functions are the first defense mechanism against various inhaled pollutants in conducting airway epithelium. Vitamin A is one of the most important factors involved in the regulation of these functions. Many studies have been carried out, but the nature of vitamin A regulation in these differentiated functions is still largely unclear. Studies with support from this grant (RO1-HL35635) have demonstrated that epithelial cells from human, monkey, and hamster tracheobronchial tissues are able to express mucous cell differentiation in culture and the differentiation is dependent on the presence of vitamin A. Without vitamin A, epithelial cells express squamous cell differentiation in culture. This competitive renewal application is concerned with the biology of mucous cell differentiation. Based on preliminary studies with the microinjection and genetic cloning, we hypothesize that vitamin A regulates mucous cell differentiation in two different stages. The first stage is a competent phase in which squamous epithelial cells become uncommitted to squamous or mucous cell differentiation after the vitamin A treatment. The second stage regards as a progressive phase in which uncommitted cells are committed to mucous cell differentiation after the vitamin A treatment. We also hypothesize that each stage involves different sets of new gene expression. It is proposed to investigate the gene expression in these two stages and to define the roles of these new genes in the regulation of mucous cell differentiation. Our specific aims are: 1) to clone and to characterize vitamin A-responsive genes with a focus on those involved in the early events and differentiation, 2) to define the level (i.e. transcription, translation) of gene expression regulated by vitamin A, 3) to determine whether these genes are necessary and sufficient for mucous cell differentiation, 4) to determine precursor-mucous cells relationship and cell type-specific gene expression in a biphasic organotypic culture system. Several vitamin A-responsive cDNA clones have been isolated and they will be used initially to define the stage of mucous cell differentiation and to elucidate the mechanism of vitamin A regulation.