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Am J Physiol Lung Cell Mol Physiol 279: L194-L200, 2000;
1040-0605/00 $5.00
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Vol. 279, Issue 1, L194-L200, July 2000

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

Randolph H. Hastings, John T. Berg, Daphne Summers-Torres, Douglas W. Burton, and Leonard J. Deftos

Research, Medicine, and Anesthesiology Services, Veterans Affairs San Diego Healthcare System, San Diego 92161-5085; and Departments of Anesthesiology and Medicine, University of California, San Diego, La Jolla, California 92093

Parathyroid hormone-related protein (PTHrP) is a growth inhibitor for alveolar 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 decreased between 4 and 8 days of hyperoxia, concurrent with increased expression 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 the fourth day of hyperoxia. Eight hours later, BrdU labeling in alveolar corner cells was 3.2 ± 0.4 cells/high-power field in hyperoxic PBS-instilled 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 due to 85% oxygen and may regulate cell proliferation.

adult respiratory distress syndrome; calcitropic hormones; growth factor receptor; type II pneumocyte


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