HYALURONAN AND ITS RECEPTORS IN BPD

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。 这一建议的中心假设是低分子量透明质酸(HA)浓度升高和肺集合素翻译后修饰是早产和机械通气相关的氧化、硝化和亚硝化应激的结果，是发展为支气管肺发育不良(BPD)之前的炎症过程的组成部分和促进因素。限制低分子HA和修饰的胶原素的产生或效果的治疗将限制BPD的发生率和/或严重程度。 建议的具体目标包括： 1.研究早产儿BPD模型中透明质酸及其受体、透明质酸合成酶和透明质酸酶在发育和出生后的表达与炎症及氧化、硝化和亚硝化指标的关系。 2.描述肺集合素氧化、硝化和亚硝化状态的变化与胎龄和早产后干预的关系。 3.确定可能的治疗方法对恒河猴BPD模型炎症、HA及其受体和表面活性物质变化的影响。

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. The central hypothesis of this proposal is that elevated concentrations of low molecular weight (LMW) Hyaluronan(HA) and post-translational modification of pulmonary collectins, occurring as a result of oxidative, nitrative and nitrosative stresses associated with preterm birth and ventilation, are integral to and promote the inflammatory process that precedes the development of bronchopulmonary dysplasia (BPD). Therapies that limit the production or effects of LMW HA and modified collectins will limit the incidence and/or the severity of BPD. The specific aims proposed were: 1. Characterize the developmental and postnatal expression of HA, its receptors, HA synthases and hyaluronidases in relation to inflammation and markers of oxidation, nitration and nitrosylation in the preterm baboon models of BPD. 2. Characterize the changes in oxidation, nitration and nitrosylation status of pulmonary collectins as a function of gestational age and postnatal interventions after preterm birth. 3. Determine the effects of potential therapies on the inflammatory, HA and its receptors and surfactant changes in the baboon BPD models.