ROLE OF BOMBESIN LIKE PEPTIDES IN LUNG DEVELOPMENT

不成熟的肺发育仍然是一个主要原因， 早产儿的发病率和死亡率。 这样做的目的 该项目是为了表征蛙皮素样肽在肺中的作用， 发展 蛙皮素样肽是一个大家族， 最初在青蛙皮肤中发现的肽，但后来发现， 在哺乳动物中分布广泛，具有很强的生理作用。 一 蛙皮素的哺乳动物同系物是胃泌素释放肽（GRP）。 的 GRP在发育中的人肺中的充分表达， GRP刺激细胞生长的能力导致了以下假设： GRP在肺发育中起着关键作用。 因为 由于缺乏良好的动物模型， 准确确定GRP在肺发育中的作用。 最近 我们的实验室已经证明，胎猴GRP表达 肺与人类的肺惊人地相似;因此， 为研究GRP在人体内的作用提供了动物模型 肺发育 我们现在已经开发出了管理GRP的方法， 胚胎猴的子宫和合适的形态学，组织学和 分子技术来确定这些治疗对 肺发育 在初步研究中，我们治疗了怀孕的 妊娠第55 - 72天的猴，给予生理盐水、GRP、GRP a 拮抗剂和NMB拮抗剂。 GRP治疗增加了肺总量 肺重 GRP拮抗剂治疗降低了总肺重量。 形态计量学分析表明，GRP治疗增加了上皮细胞的数量， 但对间充质体积没有影响。 未观察到任何影响 NMB拮抗剂。 目前正在进行进一步分析。 因此，这些初步数据的结果验证了我们的实验结果。 模型，并提供了基础，为今后的实验，以确定 蛙皮素样肽在灵长类动物肺发育中的作用。 资金 中心支持的项目出版物无

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