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。 近期 在我们的实验室证明，GRP表达在胎猴， 肺与人类的肺惊人地相似， 表征GRP在人肺中作用的动物模型 发展 使蛙皮素样肽对 肺发育的证据表明，在子宫内暴露于 尼古丁刺激胎儿GRP表达。 我们现在已经开发 在子宫内向胎猴施用GRP的方法， 向母亲施用尼古丁以模拟母亲吸烟，以及 合适的形态学、组织学和分子技术来确定 这些治疗对肺部发育的影响。 结果 这些研究可能对使用 蛙皮素样肽刺激肺发育。

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. The recent demonstration in our laboratory that GRP expression in fetal monkey lung is strikingly similar to that of humans now provides an excellent animal model to characterize the role of GRP in human lung development. Complicating the effects of bombesin-like peptides on lung development is evidence suggesting that in utero exposure to nicotine stimulates fetal GRP expression. We have now developed methods to administer GRP in utero to fetal monkeys, methods to administer nicotine to the mothers to simulate maternal smoking, and suitable morhometric, histologic and molecular techniques to determine the effects of these treatments on lung development. Results from these studies could have important implications for the use of bombesin-like peptides to stimulate lung development.