Role of proteoglycans in fetal lung maturation

婴儿出生时的存活在很大程度上取决于肺部能否成功地在空气和血液之间交换氧气和二氧化碳。为了完成这项任务，在胎儿时期，肺必须发育正常，在妊娠末期，肺必须在结构和生化上都成熟。因此，在预期出生时间之前出生的婴儿，在肺部有机会成熟之前就出生了。因此，不能呼吸是早产婴儿面临的主要问题之一就不足为奇了。在妊娠后期，肺发生了巨大的变化，以增加其交换气体的能力。空气和血流之间的表面积增加，屏障厚度减少。参与这种重塑的分子机制尚不清楚，但已知的是，对有早产风险的妇女使用皮质类固醇会导致这种屏障厚度大幅下降，并增加肺部的扩张性。该项目旨在了解妊娠后期肺部结构是如何成熟的，并确定皮质类固醇是否通过改变一种称为versican的特殊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，具有特殊的特性，可以保持水分并帮助组织周围的基质。我们认为，桃聚糖结构的改变会降低其保持水分的能力，从而减少组织体积，并导致肺内空气-血液组织屏障的减少。

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.