DEVELOPMENT OF THE LUNG--GROWTH FACTORS/T TYPE II CELLS

肺的发育——生长因子/T 型 II 细胞

• 批准号: 2519433
• 负责人: RICHARD J KING
• 金额: $ 20.05万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2519433
• 关键词: alveolar macrophages; cell differentiation; cell growth regulation; embryo /fetus; growth /development; hepatocyte growth factor; immunocytochemistry; immunoprecipitation; in situ hybridization; laboratory rat; protein biosynthesis; pulmonary surfactants; radioimmunoassay; receptor expression; transforming growth factors

DESCRIPTION (Adapted from the Investigator's Abstract): Studies of development of organ systems other than the lung during fetal life has demonstrated importance of mesenchymal-epithelial interactions wither through release of soluble growth factors or through peptides in the interstitial matrix. Preliminary work on the lung also indicates a role for mesenchymal-epithelial interactions and that cellular activities may be temporarily and specially regulated. During branching morphogenesis cellular proliferation is important whereas in later gestation differentiation of airway epithelial cells into type Two cells which synthesize pulmonary surfactant becomes crucial. This application addresses two growth factors, transforming growth factor alpha (TGF-a) and hepatocyte growth factor (HGF), with emphasis on their effects on type II cells. These factors have been chosen because 1) production by fetal lung fibroblasts is gestational age dependent, 2) both factors may stimulate surfactant synthesis in fetal type II cells, 3) fetal type II cells have HGF receptors and 4) and HGF stimulates proliferation of both fetal and type II cells in primary culture. It is hypothesized that TGF-a and HGF regulate changes in the proliferation and differentiated function of alveolar epithelial cells during fetal development contributing to regulation of surfactant in the fetus and newborn. The four Specific Aims are 1) to define the ontogeny of TGF-a and HGF production in fetal lung fibroblasts and the developmental pattern of their receptors in Type II cells; 2) Isolate and partially sequence the principal isoform of TGF-a in fetal rat lung fibroblasts; 3) To isolate the fetal isoform of TGF-a and test effects on fetal type II cell function; 4) to examine the role of protein kinase C in effects of TGF-a by using inhibitors. These studies will define expression and function of the two growth factors during fetal lung development and contribute to our understanding of the regulation of this process.

描述（改编自调查员的摘要）： 胎儿生活期间肺以外的器官系统的开发已有 表现出间质上皮相互作用的重要性 通过释放可溶性生长因子或通过肽中的肽 间质基质。 肺的初步工作也表明了 间质上皮相互作用，细胞活性可能是 暂时，特别受监管。 在分支形态发生期间 细胞增殖很重要，而后来的妊娠很重要 将气道上皮细胞分化为两个型细胞 合成的肺表面活性剂变得至关重要。 此应用程序地址 两个生长因子，转化生长因子α（TGF-A）和肝细胞 生长因子（HGF），重点是它们对II型细胞的影响。 这些 之所以选择因素，是因为1）胎儿肺成纤维细胞的产生是 妊娠年龄依赖性，2）这两个因素都可能刺激表面活性剂 胎儿II型细胞中的合成，3）胎儿II型细胞具有HGF受体 4）和HGF刺激胎儿和II型细胞的增殖 初级文化。 假设TGF-A和HGF调节了 肺泡上皮细胞的增殖和分化功能 在胎儿发育过程中，有助于调节表面活性剂 胎儿和新生儿。 四个具体目标是1）定义的个体发育 胎儿肺成纤维细胞和发育性的TGF-A和HGF产生 其受体在II型细胞中的模式； 2）隔离和部分 序列TGF-A在胎儿大鼠肺成纤维细胞中的主要同工型； 3）到 分离TGF-A的胎儿同工型，并对II型胎儿的测试影响 功能; 4）检查蛋白激酶C在TGF-A的作用中的作用 使用抑制剂。 这些研究将定义 胎儿肺发育过程中的两个增长因素，并为我们的 了解该过程的调节。