Role of proteoglycans in fetal lung maturation

蛋白多糖在胎儿肺成熟中的作用

• 批准号: nhmrc : 237103
• 负责人: Prof Amanda Fosang
• 金额: $ 17.02万
• 依托单位: Murdoch Childrens Research Institute
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2003
• 资助国家: 澳大利亚
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-proteoglycans-fetal-lung-maturation/99938
• 关键词: Role; proteoglycans; fetal; lung; maturation

The survival of a baby at birth is crtically dependent upon the ability of the lungs to successfully take over the role of exchanging oxygen and carbon dioxide between the air and blood. To perform this task, during fetal life the lung must have grown properly and near the end of gestation it must mature both structurally and biochemically. Thus, babies that are born early, before the expected time of birth, are born before the lungs have had the opportunity to mature. It is not surprising, therefore, that an inability to breathe is one of the primary problems faced by a prematurely born infant. During late gestation the lung changes dramatically in order to increase its ability to exchange gases. There is an increase in surface area and a reduction in the barrier thickness between the airspace and the blood stream. The molecular mechanisms involved in this remodelling are unknown, but it is known that the administration of corticosteroids to women at risk of preterm labour causes a large decrease in this barrier thickness and increases the distensibility of the lung. This project seeks to understand how the structure of the lung matures in late gestation and to determine whether corticosteroids regulate these changes by altering the structure of a specialised molecule, called versican. Versican resides in the tissue space outside of cells and has special properties that allow it to retain water and help organise the surrounding matrix. We propose that alterations in the structure of versican will reduce its ability to retain water, thereby reducing the tissue volume and contributing to a reduction in the air-blood tissue barrier within the lung.

婴儿出生时的存活率主要取决于肺成功地在空气和血液之间交换氧气和二氧化碳的能力。为了完成这项任务，在胎儿期，肺必须正常生长，在妊娠末期，肺必须在结构和生化方面都成熟。因此，早出生的婴儿，在预期的出生时间之前，在肺有机会成熟之前出生。因此，无法呼吸是早产儿面临的主要问题之一，这并不奇怪。在妊娠晚期，肺发生了巨大的变化，以增加其交换气体的能力。在空气空间和血流之间存在表面积的增加和屏障厚度的减少。参与这种重塑的分子机制尚不清楚，但已知对有早产风险的妇女给予皮质类固醇会导致屏障厚度大幅降低，并增加肺的扩张性。该项目旨在了解肺的结构如何在妊娠后期成熟，并确定皮质类固醇是否通过改变一种称为多功能蛋白聚糖的专门分子的结构来调节这些变化。Versican存在于细胞外的组织空间中，具有特殊的性质，使其能够保持水分并帮助组织周围的基质。我们认为，多功能蛋白聚糖结构的改变将降低其保持水分的能力，从而减少组织体积，并有助于减少肺内的空气-血液组织屏障。