REGULATION OF DIFFERENTIATION OF TRACHEOBRONCHIAL EPITHELIAL CELLS

气管支气管上皮细胞分化的调控

• 批准号: 3941508
• 负责人: A M JETTEN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 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/3941508
• 关键词: cell cycle; cell differentiation; cell growth regulation; cell population study; cell type; complementary DNA; epidermal growth factor; gel electrophoresis; gene expression; genetic library; genetic regulation; growth media; mucins; respiratory epithelium; secretion; tissue /cell culture; trachea; transforming growth factors

To study the regulation of differentiation of tracheobronchial epithelial cells we have developed an in vitro cell system using rabbit tracheal epithelial cells. We have shown that these cells, under different conditions, can express either a mucous-secretory or a squamous phenotype. Cells grown on a collagen type I gel matrix in the presence of retinoids express the mucous-secretory phenotype. Biochemical analysis of 3H-glucosamine-labelled secretory products shows the release of mucous glycoproteins. Cells grown in the absence of retinoids, either on a collagen Type I gel matrix or on collagen-fibronectin coated dishes, undergo squamous differentiation. This pathway of differentiation is a multistep process. First, cells undergo terminal cell division which is characterized by the accumulation of cells in the Go/G1 phase of the cell cycle and reduction in colony forming efficiency. Terminal cell division normally occurs at high cell density but can be induced at low density either by the removal of epidermal growth factor or by the addition of transforming growth factor beta. Terminal cell division is followed by the expression of a squamous phenotype which is characterized by the appearance of a squamous morphology and changes in several biochemical markers. The formation of cross-linked envelopes is the last stage in this terminal differentiation. The commitment to terminal cell division is insensitive to retinoids whereas the expression of the squamous phenotype is under the control of retinoids. The differential effects of retinoids on the commitment to terminal cell division and expression of the squamous phenotype indicate that the control of the two events are separable; however, other evidence shows that they are regulated in a coordinate manner. We developed a cDNA library from poly(A)+ RNA isolated from squamous differentiated cells and obtained cDNA clones that hybridize with mRNAs that are expressed in squamous differentiated cells but not in undifferentiated or retinoic acid-treated cells. Study of the regulation of these genes are in progress.

目的：探讨气管支气管上皮细胞分化的规律 上皮细胞，我们开发了一种体外细胞系统， 兔气管上皮细胞 我们已经证明这些细胞， 在不同的条件下，可以表达粘液分泌型， 或鳞状表型。 在I型胶原凝胶上生长的细胞 基质在维甲酸的存在下表达粘液分泌 表型 ~ 3 H-氨基葡萄糖标记的生化分析 分泌产物显示粘液糖蛋白的释放。 细胞在没有类维生素A的情况下生长，无论是在胶原类型 I凝胶基质或胶原-纤连蛋白包被的培养皿上， 鳞状分化 这种分化途径是一种 多步过程 首先，细胞进行终末细胞分裂 其特征在于细胞在Go/G1中的积累， 细胞周期的阶段和集落形成效率的降低。 终末细胞分裂通常发生在高细胞密度下， 在低密度下通过去除表皮 生长因子或通过加入转化生长因子 β的 终末细胞分裂后， 鳞状表型，其特征在于 鳞状形态和几种生化指标的变化 标记。 交联包膜的形成是最后一步 在这个终端的分化阶段。 的承诺 终末细胞分裂对维甲酸不敏感， 鳞状细胞表型的表达受 类维生素A。 类维生素A对神经细胞凋亡的不同影响 终末细胞分裂的承诺和表达 鳞状细胞表型表明，这两个事件的控制 是可分离的;然而，其他证据表明，它们是 以协调的方式进行管理。 我们建立了一个cDNA文库 从鳞状分化细胞分离的poly（A）+ RNA 并获得与mRNA杂交的cDNA克隆， 在鳞状分化细胞中表达，但在 未分化或视黄酸处理的细胞。 研究 这些基因的调控正在进行中。