AIRWAY REMODELING--CELL-CELL INTERACTIONS

描述：(根据申请者的抽象和具体目标改编。) 在哮喘等慢性阻塞性肺疾病中的研究报告 气道壁的结构变化，包括光滑程度的增加 肌肉发达。关于以下方面的可用信息很少 控制各种细胞质量的因素，这些细胞构成 气道壁，尚不清楚质量增加是否通过 驻留细胞的增生或肥大。的总目标是 这个项目是为了定义呼吸道上皮细胞之间的相互作用， 平滑肌细胞和成纤维细胞在细胞生长方面。整体而言 工作假说是呼吸道上皮细胞，平滑肌细胞， 成纤维细胞及其周围的基质以一种复杂的方式相互作用 这种相互作用决定了气道壁的结构。 在与呼吸道损伤相关的情况下，如高氧血症， 正常的细胞间相互作用与生长调节因子的产生 被破坏，导致呼吸道结构和功能改变。这个 具体目标是：1)比较个体的反应模式 将呼吸道器官内的细胞培养成分离的上皮细胞， 平滑肌细胞和成纤维细胞对特定生长的反应 因素：2)评估气道壁细胞间的相互作用； 3)比较呼吸道内单个细胞的反应模式 器官培养成分离的上皮细胞、平滑肌细胞 和成纤维细胞对氧损伤的反应，以及4)确定 细胞：细胞相互作用如何调节细胞对氧气的反应 致伤。这些实验可以提供重要的新见解。 探讨维持正常呼吸道的因素 结构以及与损伤和哮喘相关的重塑反应。

DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) In chronic obstructive lung diseases such as asthma studies report structural changes in the airway wall including increases in smooth muscle mass. There is little information available with respect to factors that control the mass of the various cells which constitute the airway wall and it is unclear whether increases in mass occur via hyperplasia or hypertrophy of the resident cells. The overall goal of this project is to define the interaction of airway epithelial cells, smooth muscle cells and fibroblasts in terms of cell growth. The overall working hypothesis is that airway epithelial cells, smooth muscle cells, fibroblasts and the matrix surrounding them interact in a complex fashion and this interaction is responsible for the structure of the airway wall. In conditions associated with airway injury, such as hyperoxia, the normal cell-cell interactions and production of growth modulating factors is disrupted, inducing altered airway structure and function. The Specific Aims are: 1) to compare the pattern of response of individual cells within airway organ cultures to that of isolated epithelial cells, smooth muscle cells and fibroblasts in response to selected growth factors; 2) to assess the interaction of the cells in the airway wall; 3) to compare the pattern of response of individual cells within airway organ cultures to that of isolated epithelial cells, smooth muscle cells and fibroblasts in response to oxygen induced injury, and 4) to determine how cell: cell interactions modulate the cellular response to oxygen induced injury. These experiments could provide important new insights into the factors responsible for the maintenance of normal airway structure and the remodeling response associated with injury and asthma.