ROLE OF BOMBESIN LIKE PEPTIDES IN LUNG DEVELOPMENT

未成熟的肺发育仍然是导致 早产儿的发病率和死亡率。这样做的目的是 该项目是为了表征蛙皮素样肽在肺中的作用 发展。蛙毒素样多肽是一大家族 最初以青蛙皮肤为特征的多肽，但后来发现 在哺乳动物中具有广泛的分布和强大的生理效应。一 蛙皮素在哺乳动物中的同源物是胃泌素释放肽(GRP)。这个 GRP在人肺发育过程中的表达及其意义 GRP刺激细胞生长的能力导致了这一假说 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，以前不可能 准确测定GRP在肺发育中的作用。最近 本实验室已证实GRP在胎猴体内的表达 肺与人类的肺惊人地相似；因此，胚胎猴子 为研究GRP在人体内的作用提供了一种动物模型 肺部发育。我们现在已经开发了管理GRP的方法 子宫到胚胎猴子和适当的形态测量、组织学和 用分子技术来确定这些处理的影响 肺部发育。在初步研究中，我们对孕妇进行了 妊娠55天至72天的猴子服用生理盐水、GRP、GRP 拮抗剂和NMB拮抗剂。GRP治疗增加肺总量 肺重量。GRP拮抗剂治疗可降低肺总重量。 形态计量学分析表明，GRP处理使上皮细胞数量增加 体积，但对间充质体积无影响。没有看到任何影响 和NMB的对手。进一步的分析目前正在进行中。 因此，这一初步数据的结果验证了我们的实验 模型，并为以后的实验提供了基础，以确定 蛙皮素样肽在灵长类动物肺发育中的作用。资金来源 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