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.
| Vichi, P; Whelchel, A; Knot, H et al. (1999) Endothelin-stimulated ERK activation in airway smooth-muscle cells requires calcium influx and Raf activation. Am J Respir Cell Mol Biol 20:99-105 |
| Vichi, P; Whelchel, A; Posada, J (1999) Transmembrane helix 7 of the endothelin B receptor regulates downstream signaling. J Biol Chem 274:10331-8 |
| Whelchel, A; Evans, J; Posada, J (1997) Inhibition of ERK activation attenuates endothelin-stimulated airway smooth muscle cell proliferation. Am J Respir Cell Mol Biol 16:589-96 |
| Shapiro, P S; Evans, J N; Davis, R J et al. (1996) The seven-transmembrane-spanning receptors for endothelin and thrombin cause proliferation of airway smooth muscle cells and activation of the extracellular regulated kinase and c-Jun NH2-terminal kinase groups of mitogen-activated protein kinases. J Biol Chem 271:5750-4 |
