The Role of Elastin and Elastic Fiber-Related Proteins in Vascular Development, Function and Homeostasis

血管壁的形成是一个复杂、协调的过程。大血管必须具有伸展和回缩的能力，以适应血液从心脏排出时的脉动。负责这一特征的蛋白质是弹性蛋白。弹性蛋白由壁中的肌肉细胞分泌，并组装成片状或片层，与细胞交替形成多层。多年来，已发现大量蛋白质参与弹性膜的组装，然而，每种蛋白质的具体功能仍有待确定。了解蛋白质功能的一种方法是制造一只缺少感兴趣蛋白质的小鼠。通过研究这种被称为基因敲除小鼠的组织的超微结构，人们可以开始描述被敲除的蛋白质在组织组装和/或功能中的作用。在弹性纤维生物学领域，各个研究小组已经制造了大量的基因敲除小鼠。大多数情况下，对这些小鼠体内富含弹性蛋白的组织，如血管、肺和皮肤，还没有进行详细的分析，从他们的研究中还可以获得更多新的和重要的信息。在我们的研究计划中，我们将研究几种不同的小鼠模型来研究纤维蛋白-1和纤维蛋白-4，这两种蛋白质对弹性膜的形成至关重要。我们还将创建一个新的弹性蛋白小鼠模型，这将使我们能够了解哪些细胞对血管发育至关重要，以及这些细胞如何将弹性蛋白组装成弹性板。弹性蛋白是一种独特的蛋白质，因为它只在青春期形成，在此之后不会产生新的弹性蛋白。因此，血管中弹性膜和肺部和皮肤中弹性纤维的适当组装是一个关键过程，因为我们生命早期产生的弹性蛋白必须持续一生。因此，我们的长期目标是了解弹力板和弹性纤维是如何在组织中组装的，以及这些结构在受伤或疾病中可能会如何受损。

The formation of a blood vessel wall is a complex, coordinated process. Large vessels must have the ability to stretch and recoil to accommodate the pulsation of the blood as it is ejected from the heart. The protein responsible for this feature is elastin. Elastin is secreted by the muscle cells in the wall and assembled into sheets or laminae that alternate with the cells to form multiple layers. Over the years, a large number of proteins have been found to contribute to the assembly of elastic laminae, however, the specific function of each of these proteins remains to be determined. One method to learn about the function of a protein is to make a mouse that is missing the protein of interest. By studying the ultrastructure of the tissues in such mice, called knockout mice, one can begin to delineate the role of the knocked out protein in tissue assembly and/or function. In the field of elastic fiber biology, a large number of knockout mice have already been made by various research groups. For the most part, a detailed analysis of the elastin-rich tissues in these mice, such as blood vessels, lungs and skin, has not been conducted and there is additional novel and important information to be obtained from their study. In our research program, we will study several different mouse models for fibrillin-1 and fibulin-4, two proteins that are critical for elastic laminae formation. We will also generate a new mouse model for elastin, which will provide us with the ability to learn what cells are important for blood vessel development and how the cells assemble the elastin into the elastic laminae. Elastin is a unique protein, in that, it is only made up to young adulthood, after which time, no new elastin is produced. The proper assembly of elastic laminae in blood vessels and elastic fibers in lungs and skin is therefore a critical process since the elastin we produce early in our lives must last a lifetime. Thus, it is our long-term goal to understand how elastic laminae and elastic fibers are assembled in tissues, and how these structures may be damaged in injury or disease.