Parathyroid Hormone–Related Protein in the Healthy and Injured Lung

Abstract

Parathyroid hormone–related protein (PTHrP) is an oncofetal protein with functional effects in normal and diseased lung. In the respiratory system, the hormone has implications for a variety of processes, including lung development, alveolar type II cell function and differentiation, cell proliferation, apoptosis, motility, and matrix interactions. PTHrP regulates branching morphogenesis and type II cell maturation in fetal lung through bidirectional interactions with lung fibroblasts. Consequently, it appears to have a role in the pathophysiology of respiratory distress syndrome and bronchopulmonary dysplasia. In adult lung, the molecule has autocrine actions on type II pneumocytes that stimulate phosphatidylcholine production, inhibit cell proliferation, and sensitize to apoptotic stimuli. Type II cell PTHrP levels fall after lung injury, inversely coordinated in time with their proliferation, suggesting that reduction in its growth inhibitory effect may contribute to the increase in type II cell numbers after injury. Air space levels of the protein are inversely related to the risk of lung injury or injury severity in neonatal and adult lung, consistent with its production by pneumocytes. Thus, PTHrP has clinical significance as a biomarker for injury and as a potential target for treatment.