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

弹性蛋白和弹性纤维相关蛋白在血管发育、功能和稳态中的作用

• 批准号: 355710-2013
• 负责人: Davis, Elaine
• 金额: $ 2.19万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=527867
• 关键词: Role; Elastin; Elastic; Fiber; Related

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.

血管壁的形成是一个复杂的、协调的过程。 大血管必须具有伸展和回缩的能力，以适应血液从心脏喷出时的脉动。 负责这一功能的蛋白质是弹性蛋白。 弹性蛋白由壁中的肌细胞分泌，并组装成与细胞交替形成多层的片或层。 多年来，大量的蛋白质被发现有助于弹性层的组装，然而，这些蛋白质中的每一个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失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小鼠组织的超微结构，人们可以开始描述基因敲除蛋白在组织组装和/或功能中的作用。 在弹性纤维生物学领域，各研究小组已经制造出大量基因敲除小鼠。 在大多数情况下，尚未对这些小鼠中富含弹性蛋白的组织（如血管，肺和皮肤）进行详细分析，并且还需要从他们的研究中获得额外的新的重要信息。 在我们的研究计划中，我们将研究几种不同的小鼠模型，用于研究弹性膜层形成关键的两种蛋白质--fibulin-1和fibulin-4。 我们还将为弹性蛋白生成一个新的小鼠模型，这将使我们能够了解哪些细胞对血管发育很重要，以及细胞如何将弹性蛋白组装成弹性膜。 弹性蛋白是一种独特的蛋白质，因为它只在年轻时形成，之后不会产生新的弹性蛋白。 因此，血管中的弹性层和肺部和皮肤中的弹性纤维的正确组装是一个关键过程，因为我们在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性层和弹性纤维如何在组织中组装，以及这些结构如何在损伤或疾病中受损。