NICOTINE AND ALPHA7 NICOTINIC RECEPTORS IN LUNG DEVELOPMENT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 根据美国疾病控制与预防中心的最新统计数据，1999年，12.3%的美国妇女在怀孕期间吸烟，相当于超过40万名婴儿暴露在烟雾中。孕期吸烟是导致低出生体重、早产、新生儿发病率和死亡率的最大可预防原因。此外，据估计，10%的胎儿和新生儿死亡是由于怀孕期间吸烟造成的。怀孕期间吸烟直接和不利地影响肺部发育，表现为吸烟母亲所生子女的肺功能改变和呼吸道疾病增加。值得注意的是，吸烟是如何产生这些影响的尚不清楚。虽然母亲吸烟造成肺损伤的原因可能是多因素的，但该项目的假设是，母亲吸烟对肺的部分影响是通过尼古丁通过胎盘与发育中的肺中的α7尼古丁受体相互作用而介导的。在这个项目中，将使用功能小鼠的Alpha7基因敲除和Alpha7获得来研究产前尼古丁暴露和Alpha7 nAChR之间的联系。根据我们的初步数据和人类婴儿的流行病学数据，我们将重点讨论吸烟对肺发育的三个方面的影响：通过主动和被动试验测量的肺功能、细胞生长和胶原蛋白的表达。这些研究将对怀孕期间吸烟对肺部发育影响的分子机制做出一些初步解释。了解这些机制可能会导致阻断怀孕期间吸烟影响的治疗。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. According to the latest statistics from the CDC, in 1999, 12.3% of American women smoked during pregnancy, translating to over 400,000 smoke-exposed infants. Smoking during pregnancy is the largest preventable cause of low birth weight, premature delivery, neonatal morbidity and mortality. Further, it has been estimated that 10% of all fetal and neonatal deaths are due to smoking during pregnancy. Smoking during pregnancy directly and adversely affects lung development as manifested by altered pulmonary function and increased respiratory illness in children born of smoking mothers. Remarkably, how smoking produces these effects is unknown. While the cause of pulmonary damage caused by maternal smoking is likely to be multifactorial, it is the hypothesis of this project that part of the effect of maternal smoking on lung is mediated by nicotine transported across the placenta to interact with alpha7 nicotinic receptors in developing lung. In this project, alpha7 knockout and alpha7 gain of function mice will be used to study the link between the effects of prenatal nicotine exposure and alpha7 nAChR. Based on our preliminary data and epidemiologic data on human infants, we will focus on 3 aspects of smoking's effects on lung development: pulmonary function as measured by active and passive tests, cell growth, and collagen expression. From these studies will come some of the first explanations of the molecular mechanisms that underlie the effects of smoking during pregnancy on lung development. Understanding these mechanisms may lead to therapies to block the effects of smoking during pregnancy.