SURFACTANT PROTEIN REGULATION IN DEVELOPING LUNG

肺表面活性物质的主要功能是降低表面活性剂的浓度， 肺中的气液界面处的张力，从而防止 低肺容量时肺泡萎陷。 表面活性剂生产不足 毫无疑问与呼吸窘迫综合征（RDS）有关， 新生儿 表面活性剂是磷脂的复杂组合， 胆固醇和肺特异性表面活性蛋白的三个家族。 的 最丰富的表面活性蛋白是一种糖蛋白， 分子量降低到26-38 KDa，被命名为SP-A。 剩下的两 表面活性剂蛋白是非常疏水的。 这两种蛋白质的分子量为 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，这三个影响表面 表面活性剂磷脂的张力降低特性。 由于RDS是一个 表面活性剂缺乏引起的病症，了解 调节这些表面活性剂蛋白的表达显然是重要的。 本提案的目的是确定影响启动的因素 三种表面活性蛋白在预分化的 肺，沿着的因素，导致表达的加速，可以是 分为三大类：激素和其他可溶性因子， 上皮细胞-细胞外基质相互作用，以及上皮- 间充质相互作用 我们将评估胎儿肺细胞对 这些因素通过几种方法。 这些将包括定量 表面活性剂蛋白及其mRNAsl的含量， 表面活性剂蛋白质合成，测定特定 表面活性剂蛋白。 本项目的总体目标是确定 内分泌和旁分泌影响调节SP-A，SP-B， 和SP-C在发育中的肺中。 了解表面活性蛋白 可能导致新的预防和治疗方法 的RDS。

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.