Parathyroid hormone-related protein reduces alveolar epithelial cell proliferation during lung injury in rats

Parathyroid hormone-related protein (PTHrP) is a growth inhibitor for alveo lar type II cells and could be a regulatory factor for alveolar epithelial cell proliferation after lung injury. We investigated lung PTHrP expression in rats exposed to 85% oxygen. Lung levels of PTHrP were significantly dec reased between 4 and 8 days of hyperoxia, concurrent with increased express ion of proliferating cell nuclear antigen and increased incorporation of 5- bromo-2'-deoxyuridine (BrdU) into DNA in lung corner cells. PTHrP receptor was present in both normal and hyperoxic lung. To test whether the fall in PTHrP was related to cell proliferation, we instilled PTHrP into lungs on t he fourth day of hyperoxia. Eight hours later, BrdU labeling in alveolar co rner cells was 3.2 +/- 0.4 cells/high-power field in hyperoxic PBS-instille d rats compared with 0.5 +/- 0.3 cells/high-power field in PTHrP-instilled rats (P< 0.01). Thus PTHrP expression changes in response to lung injury du e to 85% oxygen and may regulate cell proliferation.