NICOTINE AND ALPHA7 NICOTINIC RECEPTORS IN LUNG DEVELOPMENT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 根据疾病预防控制中心的最新统计数据，1999年，12.3%的美国女性在怀孕期间吸烟，导致超过40万名婴儿接触烟雾。怀孕期间吸烟是造成出生体重不足、早产、新生儿发病和死亡的最大可预防原因。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。怀孕期间吸烟直接对肺部发育产生不利影响，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，吸烟如何产生这些影响尚不清楚。虽然母亲吸烟引起的肺损伤可能是多因素的，但本项目的假设是，母亲吸烟对肺的部分影响是通过尼古丁通过胎盘转运与发育中的肺中的α 7烟碱受体相互作用介导的。在该项目中，alpha 7基因敲除和alpha 7功能获得小鼠将用于研究产前尼古丁暴露与alpha 7 nAChR影响之间的联系。基于我们的初步数据和人类婴儿的流行病学数据，我们将重点关注吸烟对肺发育的影响的3个方面：通过主动和被动测试测量的肺功能，细胞生长和胶原蛋白表达。从这些研究中，将首次解释怀孕期间吸烟对肺部发育影响的分子机制。了解这些机制可能会导致治疗，以阻止怀孕期间吸烟的影响。

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.