REGULATION OF EXPRESSION OF AMINOPEPTIDASE-N IN FETAL-RAT LUNG BY DEXAMETHASONE AND EPIDERMAL GROWTH-FACTOR

Aminopeptidase N (EC 3.3.11.2) (APN) is an ectopeptidase expressed in lung at the apical surface of alveolar type II epithelial cells. Its expression is up-regulated during fetal lung development. Recently several ectopeptidases have been recognized as possible regulators of growth and cell differentiation through their role in hydrolysis of autocrine and paracrine peptides that influence these processes. The studies reported here describe effects of factors known to promote lung development and differentiation of the alveolar epithelium on expression of aminopeptidase N during fetal lung development in organ culture. Fetal rat lung was placed in organ culture at the 15th gestational day and cultured for 6 days in the presence or absence of the synthetic glucocorticoid hormone dexamethasone or epidermal growth factor (EGF). Steady-state levels of APN mRNA increased approximately 10-fold during the 6-day culture. During this time the lung alveolar epithelium developed to the point where immature alveolar type II: cells were recognized by the presence of lamellar bodies. Dexamethasone or EGF increased the levels of APN mRNA in the fetal lung 2-to 3-fold over control cultures by the third day in culture and concurrently accelerated the morphological development of the alveolar epithelium. Differences in treated and control cultures diminished after 6 days in culture when the epithelium appeared more mature, suggesting that the immature epithelium was more responsive to the treatments.