LUNG ALVEOLAR EPITHELIAL CELL DIFFERENTIATION

已知间质-上皮相互作用是细胞增殖所必需的。 胎儿肺的形态发生。 间质-上皮相互作用可能 部分由细胞外基质介导。 我们假设 细胞外基质组成和结构的变化 先于或伴随胎肺分化 肺泡上皮细胞 最近，转化生长因子β（TGF β），一种生长因子， 已知调节细胞外基质组成，已显示 抑制SP-A的表达，SP-A是一种表面活性剂相关蛋白， 在分化的II型细胞中合成。 相反，表皮生长 EGF是另一种已知调节细胞外基质的生长因子 产生，增加SP-A的表达，刺激肺 成熟 我们建议本地化和评估的水平变化， TGF β和EGF或其同系物TGF α在胎儿发育过程中 应用形态学和分子生物学方法研究兔肺的体内成熟 技术. 我们将描述这些生长因子对 家兔细胞外基质的结构和组成 在外植体中分化。 我们以前已经证明，胎儿肺 纤维连接蛋白浓度在肺泡上皮细胞 分化 我们建议通过确定 TGF β和EGF对纤维连接蛋白mRNA水平以及 纤连蛋白受体的mRNA水平。 最后，我们建议 评估细胞外的纤连蛋白受体的mRNA的影响。 最后，我们建议评估细胞外基质的影响， 组分对纯化的II型细胞中分化维持的作用 维持在单层培养中。 我们会把细胞外基质- 诱导细胞骨架和细胞形状的变化到II型的程度 体外细胞分化，特别是关于表达 的SP-A。 因此，我们将记录两种基因的分布、mRNA水平和作用。 生长因子TGF β和EGF。 我们假设 这些生长因子影响肺的机制之一 成熟包括调节组织的组成和结构， 细胞外基质 因此，我们将记录这些影响 生长因子对细胞外基质成分代谢的影响。 的 我们的研究结果将增加有关的作用， 细胞外基质在调节细胞分化中的作用， 生长因子在调节胎儿肺发育中的作用。

Mesenchymal-epithelial interactions are known to be required for the morphogenesis of the fetal lung. Mesenchymal-epithelial interactions may be mediated, in part, by the extracellular matrix. We hypothesize that changes in the composition and structure of the extracellular matrix precede, or else are concomitant with the differentiation of fetal lung alveolar epithelial cells. Recently, transforming growth factor beta (TGFbeta), a growth factor that is known to regulate extracellular matrix composition, has been shown to inhibit the expression of SP-A, a surfactant-associated protein that is synthesized in differentiated type II cells. Conversely, epidermal growth factor, (EGF), another growth factor known to regulate extracellular matrix production, increases the expression of SP-A and stimulates lung maturation. We propose to localize and evaluate changes in the levels of TGFbeta and EGF, or its homologue, TGFalpha, during the course of fetal rabbit lung maturation in vivo using morphological and molecular biology techniques. We will characterize the effects of these growth factors on the structure and composition of the extracellular matrix in rabbit differentiation in the explants. We have shown previously that fetal lung fibronectin concentrations increase at the time of alveolar epithelial cell differentiation. We propose to extend these studies by determining the effects of TGFbeta and EGF on the levels of fibronectin mRNA as well as on the levels of mRNA for the fibronectin receptor. Finally, we propose to evaluate the effects of extracellular of mRNA for the fibronectin receptor. Finally, we propose to evaluate the effects of extracellular matrix components on the maintenance of differentiation in purified type II cells maintained in monolayer culture. We will relate extracellular matrix- induced changes in the cytoskeleton and cell shape to the degree of type II cell differentiation in vitro, in particular with respect to the expression of SP-A. Thus, we will document the distribution, levels of mRNA, and actions of two growth factors TGFbeta and EGF, in fetal lung tissue. We hypothesize that one of the mechanisms by which these growth factors act to influence lung maturation involves the regulation of the composition and structure of he extracellular matrix. Therefore, we will document the effects of these growth factor on the metabolism of extracellular matrix components. The results of our studies will increase knowledge concerning the role of the extracellular matrix in the regulation of cell differentiation a well as the role of growth factors in the regulation of fetal lung development.