REGULATION OF ALVEOLAR EPITHELIAL CELL DIFFERENTIATION

肺泡上皮细胞分化的调节

基本信息

批准号：
2221034
负责人：
ROY A LEVINE
金额：
$ 18.29万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-07-01 至 1995-03-31
项目状态：
已结题

项目摘要

We have as our goal, characterization of the process of alveolar epithelial cell differentiation and an understanding of the molecular mechanisms by which this differentiation is regulated. Differentiation for the purposes of this proposal is considered in the broadest sense, to include features of the type 2 cell which do not relate to surfactant synthesis per se as well as the capacity of the cell to undergo cell proliferation and features of the alveolar type 1 cell. We have developed a panel of alveolar epithelial cell differentiation markers which allow us to evaluate transcription and translation of cell-specific genes and their products. We also have preliminary information relating to control of type 2 cell proliferation and have designed experiments and assembled probes which will provide a unique opportunity to study mechanisms of epithelial cell growth control and the relation of proliferation to differentiation in lung epithelial cells. A focus of these studies will be an investigation of developmentally regulated growth suppression genes. This proposal utilizes two lung-derived epithelial cell systems which proliferate and can be induced to differentiate in vitro. The first cell system, peripheral lung epithelial cells isolated from the 18 day fetus at an early stage of epithelial cell differentiation, has been developed and partially characterized in our laboratory. The second cell system is a new genetically engineered type 2 cell construct, which has been developed in our laboratory. This immortalized cell line, produced by transfection of type 2 cells with the E1A-12s adenovirus gene, constitutively produces surfactant apoprotein A (SPA) and can be induced to express other features of differentiation. It provides a means of exploring the molecular mechanisms involved in developmentally regulated SPA induction and this information can in turn be used to investigate basic mechanisms that regulate differentiation of other features of the alveolar epithelium.

我们的目标是肺泡过程的表征上皮细胞分化和对通过调节这种分化的分子机制。考虑到本提案的目的差异化最广泛的意义，包括2型单元格的特征与表面活性剂的合成本身无关细胞的能力经历细胞增殖和特征牙槽1型细胞。我们已经开发了一个肺泡面板上皮细胞分化标记，使我们能够评估细胞特异性基因及其的转录和翻译产品。我们也有与控制有关的初步信息 2型细胞增殖，并设计了实验和组装探测器将为学习提供独特的机会上皮细胞生长控制的机制和肺上皮细胞分化的增殖。重点这些研究将是对发展的研究调节生长抑制基因。该建议利用两个肺衍生的上皮细胞系统，可以增殖并可以是诱导分化体外。第一个单元系统，从18天胎儿分离出的外周肺上皮细胞上皮细胞分化的早期阶段已经在我们的实验室中开发并部分表征。这第二个细胞系统是一种新的基因工程2型细胞构造，这是在我们的实验室中开发的。这永生的细胞系，通过转染2型细胞产生使用E1A-12S腺病毒基因，组成性产生表面活性剂载蛋白A（SPA），可以诱导表达其他差异化的特征。它提供了一种探索与发育调节的水疗中有关的分子机制归纳和这些信息又可以用于调查调节其他特征差异化的基本机制牙槽上皮的。