Type II cells are of critical importance for alveolar function. The produce pulmonary surfactant, they expression ion pumps that clear liquid from the alveolar space, and they are pluripotential cells that can divide and differentiate into type I cells in the setting of acute lung injury. Parathyroid hormone-related protein (PTHrP) is an autocrine regulator of type II cell function, proliferation and apoptosis. Alteration of PTHrP expression appears to be a general mechanism regulating the type II cell response to various forms of lung injury, including chronic hyperoxia, acute hyperoxia, sillica, and reperfusion injury. This project centers on the hypothesis that changes in expression of PTHrP. during acute lung injury mediate effects on type II cell function, growth and apoptosis.
The Specific Aims are (1) to investigate the cause-effect relationship between PTHrP and changes in type II cell function, proliferation relationship between PTHrP and changes in type II cell function, proliferation and apoptosis during acute lung injury; (2) to investigate PTHrP as a measure and apoptosis during acute lung injury; (2) to investigate PTHrP as a measured of type II cell function and growth during acute lung injury; (3) to study expression of function-, cell cycle- and apoptosis-related genes during lung injury and to determine whether expression of these genes can be altered by manipulating lung PTHrP levels; and (4) to investigate the interactions of PTHrP with other growth factors during lung injury.
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