SURFACTANT PROTEIN REGULATION IN DEVELOPING LUNG

肺表面活性物质起着降低体表的主要作用 肺内气液界面的张力，从而防止 低肺容量时肺泡塌陷。表面活性物质生产中的不足 已经无可争辩地与呼吸窘迫综合征(RDS)有关 新生儿。表面活性剂是磷脂的复杂组合， 胆固醇，以及三个肺特异性表面活性物质蛋白家族。这个 最丰富的表面活性蛋白是一种糖蛋白，具有 相对分子质量为26-38 KDa，已被指定为SP-A。剩下的两个人 表面活性蛋白质是非常疏水的。这两种蛋白质的相对分子质量为 18 kDa和5-8 kDa，分别命名为SP-B和SP-C。 虽然表面活性蛋白的全部功能尚不清楚 准确地说，已经证明了这三种物质都会影响表面。 表面活性剂磷脂的降张性能。由于RDS是一种 由表面活性物质缺乏引起的情况，了解 调节这些蛋白质的表面活性物质的表达显然很重要。 这项建议的目的是确定影响启动的因素 三种表面活性物质蛋白在预分化卵巢癌中的表达 肺，以及导致加速表达的因素可以是 分为三大类：荷尔蒙和其他可溶性因子， 上皮细胞-细胞外基质的相互作用，以及上皮- 间充质相互作用。我们将评估胎肺细胞对 这些因素通过几种方法得到。这些措施将包括量化 表面活性蛋白及其mRNAS1含量的测定 表面活性蛋白质合成，特定的相对速率的测定 表面活性蛋白质。这个项目的总体目标是确定 哪些内分泌和旁分泌影响调节SP-A、SP-B、 和发育中的肺组织中的SP-C。关于表面活性物质蛋白质如何 可能会导致新的预防和治疗方法 RDS的。

Pulmonary surfactant serves the primary function of lowering surface tension at the air-liquid interface in the lung, thereby preventing alveolar collapse at low lung volumes. Deficiency in surfactant production has been incontrovertibly linked to respiratory distress syndrome (RDS) in the neonate. Surfactant is a complex combination of phospholipids, cholesterol, and three families of lung-specific surfactant proteins. The surfactant protein found in greatest abundance is a glycoprotein of with a reduced MW of 26-38 KDa that has been designated SP-A. The two remaining surfactant proteins are very hydrophobic. These two proteins have MWs of 18 KDa and 5-8 kDa, and have been designated SP-B and SP-C, respectively. While the full range of functions of the surfactant proteins are not known precisely, it has been demonstrated that all three affect the surface tension-lowering properties of surfactant phospholipids. Since RDS is a condition caused by surfactant deficiency, understanding the factors that regulate expression of these proteins of surfactant in clearly important. The intent of this proposal is to determine the factors affect initiation of expression of the three surfactant proteins in the predifferentiated lung, along with the factors that cause acceleration of expression can be divided into three general groups: hormones and other soluble factors, epithelial cell-extracellular matrix interactions, and epithelial- mesenchymal interactions. We will evaluate response of fetal lung cells to these factors by several methods. These will include quantitation of content of the surfactant proteins and their mRNAsl, measurement of surfactant protein synthesis, determination of relative rates of specific surfactant proteins. The overall goal of this project is to determine which endocrine and paracrine influences regulate expression of SP-A, SP-B, and SP-C in the developing lung. Knowledge of how the surfactant proteins are regulated may result in new approaches for the prevention and treatment of RDS.