AIRWAY REMODELING--CELL-CELL INTERACTIONS

描述：（改编自申请人的摘要和具体目标。） 在慢性阻塞性肺病如哮喘研究报告 气道壁的结构变化，包括平滑 肌肉质量. 关于以下方面的资料很少： 控制构成细胞的各种细胞质量的因素 气道壁，尚不清楚是否通过 驻留细胞的增生或肥大。 的总目标 这个项目是为了定义 气道上皮细胞， 平滑肌细胞和成纤维细胞在细胞生长方面。 整体 工作假设是气道上皮细胞，平滑肌细胞， 成纤维细胞和它们周围的基质以复杂的方式相互作用 并且这种相互作用是气道壁结构的原因。 在与气道损伤相关的情况下，例如高氧， 的 正常的细胞-细胞相互作用和生长调节因子的产生 被破坏，引起气道结构和功能的改变。 的 具体目的是：1）比较个体的反应模式 气道器官培养物内的细胞与分离的上皮细胞的细胞相比， 平滑肌细胞和成纤维细胞对选择性生长 （2）评价因素 气道壁细胞的相互作用; 3)比较气道内单个细胞的反应模式， 器官培养物与分离的上皮细胞、平滑肌细胞 和成纤维细胞对氧诱导损伤的反应，以及4）确定 细胞间相互作用如何调节细胞对氧气的反应 诱导损伤。 这些实验可以提供重要的新见解 负责维持正常气道的因素 结构和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.