EXTRACELLULAR MATRIX BIOLOGY OF FIBULIN-1

纤维蛋白-1是近年来发现的一种新型细胞外基质和血液蛋白 发现是结缔组织弹性纤维的一种成分 富含皮肤、肺和血管等组织。目标 在本申请中提出的实验的目的是确定功能 纤维蛋白-1作为一种细胞外基质和血液蛋白的上下文。第一 具体的目标是确定解释 其与结缔组织弹性纤维的相关性及测定 纤溶蛋白-1是否在纤维化形成过程中起作用。在……里面 此外，还将进行实验，以确定是否有任何 许多涉及弹性纤维的结缔组织疾病是由 纤维蛋白-1表达或功能异常。这样做的第二个目的是 申请寻求确定纤维蛋白-1是否在这一过程中发挥作用 止血，因为它促进了血小板的黏附和扩散，是一种 血管内皮下基质的组成部分，与纤维蛋白原结合。 将进行研究，以了解纤溶蛋白-1在 导致血小板结合的主要黏附事件 内皮下细胞外基质，鉴定血小板表面分子(S) 调节与纤维蛋白-1的相互作用，并确定纤维蛋白-1 通过其促进纤维蛋白凝块的形成和稳定 与纤维蛋白的相互作用。在拟议的研究中，重点放在 在血管系统中确定纤溶蛋白-1的功能 然而，考虑到 这种新的蛋白质在其他结缔组织中广泛表达。

Fibulin-1 is a novel extracellular matrix (ECM) and blood protein recently found to be a component of connective tissue elastic fibers which are abundant in tissues such as skin, lung and blood vessels. The objectives of experiments proposed in this application are to determine the function of fibulin-1 in its context as an EcM and blood protein. The first specific aim is to identify the molecular interactions that account for its association with connective tissue elastic fibers and to determine whether fibulin-1 plays a role in the process of fibrogenesis. In addition, experiments will be performed to determine whether any of the many connective tissue diseases that involve elastic fibers are caused by abnormalities in fibulin-1 expression or function. The second aim of this application seeks to determine whether fibulin-1 has a role in the process of hemostasis since it promotes platelet adhesion and spreading, is a component of the vascular subendothelial matrix, and binds to fibrinogen. Studies will be done to gain an understanding of the role of fibulin-1 in the primary adhesion events that lead to platelet binding to subendothelial ECM, to identify the platelet surface molecule(s) that mediates interaction with fibulin-1 and to determine if fibulin-1 contributes to fibrin clot formation and stabilization through its interaction with fibrin. In the proposed research, an emphasis is placed on determining the function of fibulin-1 in the context of the vasculature however, the findings are expected to have broader implications given the widespread expression of this novel protein,in other connective tissues.