Immature lung development continues to be a major cause of morbidity and mortality in premature infants. The purpose of this project is to characterize the role of bombesin-like peptides in lung development. The bombesin-like peptides are a large family of peptides originally characterized in frog skin, but later found to have wide distribution and potent physiologic effects in mammals. One mammalian homolog of bombesin is gastrin-releasing peptide (GRP). The well documented expression of GRP in developing human lung and the ability of GRP to stimulate cellular growth has led to the hypothesis that GRP plays a critical role in lung development. Because of the lack of good animal models, it has not previously been possible to accurately determine the role of GRP in lung development. Recently our laboratory has demonstrated that GRP expression in fetal monkey lung is strikingly similar to that of humans; thus, the fetal monkey provides an animal model to charac terize th e role of GRP in human lung development. We have now developed methods to administer GRP in utero to fetal monkeys and suitable morphometric, histologic and molecular techniques to determine the effects of these treatments on lung development. In preliminary studies we have treated pregnant monkeys from day 55 to 72 of gestation with saline, GRP, a GRP antagonist and a NMB antagonist. GRP treatment increased lung total lung weight. GRP antagonist treatment decreased total lung weight. Morphometric analysis showed that GRP treatment increased epithelial volume but had no effect on mesenchymal volume. No effects were seen with the NMB antagonist. Further analyses are currently in progress. Thus the results from this preliminary data validates our experimental model and provides the basis for future experiments to determine the role of bombesin-like peptides in primate lung development. FUNDING Center-supported project PUBLICATIONS None
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