MOLECULAR EVENTS IN AIRWAY CILIATED CELL DIFFERENTIATION DURING DEVELOPMENT

发育过程中气道纤毛细胞分化的分子事件

• 批准号: 3736127
• 负责人: MARGARET W LEIGH
• 金额: --
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3736127
• 关键词: binding proteins; biomarker; cell differentiation; cilium; complementary DNA; dynein ATPase; ferrets; gene expression; genetic library; growth factor receptors; histogenesis; human genetic material tag; human subject; hybridomas; immunocytochemistry; in situ hybridization; insulinlike growth factor; messenger RNA; molecular cloning; protein biosynthesis; regeneration; respiratory epithelium; trachea; tubulin; virus receptors

Ciliated cells of airways surface epithelium function to clear inhaled particles and mucous secretions from the lungs. Either a low density of ciliated cells or aberrations in ciliary ultrastructure can impair mucociliary clearance. Although the morphology of airway ciliation during maturation and repair has been described, little is known about the molecular events involved in ciliogenesis. In humans, airway ciliation occurs prenatally; however, the majority of ciliation occurs postnatally in the ferret which has become an important study model. In these studies, we will identify or clone molecular markers for studying ciliogenesis. We will focus on three possible markers: the influenza virus receptor microtubules and dynein which is the enzyme responsible for ciliary motility. We will characterize the expression of the mRNAs for these markers at different maturational stages in the infant ferret using Northern hybridization and in situ hybridization analyses. These studies will then be carried out in ferrets after injury to the airways to determine if reciliation after injury is different from ciliation during normal development. Finally, we use these probes and techniques to define ciliation in human airways both during normal fetal maturation and following injury. These studies will be coordinated with analysis of ultrastructural features to determine the sequence of ultrastructural and morphologic events in ciliogenesis. We hypothesize that the molecular events in ciliogenesis occur in an orderly sequence and that aberrations in cilia noted after injury can be explained by interference with this process.

气道表面上皮纤毛细胞的功能是清除吸入的 颗粒和肺部的粘液分泌物。 要么是低密度的 纤毛细胞或纤毛超微结构的畸变可损害 粘膜纤毛清除率 虽然在呼吸道纤毛的形态， 成熟和修复已经描述，很少有人知道， 参与纤毛发生的分子事件。 在人类中， 发生在产前;然而，大多数纤毛形成发生在产后， 雪貂已经成为重要的研究模型。 在这些研究中，我们 将鉴定或克隆研究纤毛发生的分子标记。 我们 将集中在三个可能的标记：流感病毒受体 微管和动力蛋白是负责纤毛的酶 能动性 我们将表征这些基因的mRNA表达， 标记在不同的成熟阶段，在婴儿雪貂使用 北方杂交和原位杂交分析。 这些研究 然后在气管受伤后在雪貂身上进行， 确定受伤后的再愈合是否与受伤期间的再愈合不同 正常发展。 最后，我们使用这些探测器和技术来定义 在正常的胎儿成熟期间， 受伤后。 这些研究将与以下分析相协调： 超微结构特征，以确定超微结构和 纤毛发生中的形态学事件。 我们假设， 纤毛发生中的事件以有序的顺序发生， 损伤后注意到的纤毛可以解释为干扰了这一点， 过程