SPARC AS A REGULATOR OF VEGF ACTIVITY

血管生成是指从原有血管中生成新的血管系统，在许多生理过程和病理事件中起着至关重要的作用。对血管生成如何在组织中被调节的理解的增加将有助于各种生物和医学领域。细胞外基质（ECM）和在ECM中发现的基质细胞蛋白通过与内皮细胞和控制血管发育的血管生成因子的相互作用，作为血管生成的重要调节因子。SPARC（分泌蛋白，酸性且富含半胱氨酸）是一种基质细胞蛋白，最近被证明与血管内皮生长因子（VEGF）相互作用并调节其活性，VEGF是正常和病理情况下血管生成的主要刺激物。了解ECM中与VEGF相互作用的蛋白质及其调节VEGF活性的能力将有助于我们理解VEGF诱导的血管生成及其在组织稳态和病理中的作用。在这个应用中，我将进一步描述SPARC和VEGF的相互作用。将确定SPARC阻断VEGF激活VEGFR1和VEGFR2的能力，并检查SPARC调节VEGF活性的能力，包括内皮细胞的迁移、巨噬细胞的趋化性和血管通透性。

Angiogenesis, the development of new vasculature from preexisting blood vessels, plays a critical role in many physiological processes and pathological events. An increased understanding of how angiogenesis is regulated in tissues would contribute to a variety of biological and medical areas. The extracellular matrix (ECM) and matricellular proteins found in the ECM function as important regulators of angiogenesis by their interaction with endothelial cells and the angiogenic factors that control blood vessel development. SPARC (secreted protein, acidic and rich in cysteine), a matricellular protein, has recently been shown to interact with and regulate the activity of vascular endothelial growth factor (VEGF), a primary stimulant of angiogenesis in both normal and pathological situations. An understanding of the proteins in the ECM that interact with VEGF and their ability to regulate VEGF activity would contribute to our understanding of VEGF-induced angiogenesis and its role in tissue homeostasis and pathology. In this application I will characterize further the interaction of SPARC and VEGF. The ability of SPARC to block VEGF from activating VEGFR1 an VEGFR2 will be determined and the ability of SPARC to regulate VEGF activities including: migration of endothelial cells, chemotaxis of macrophages, and vascular permeability will be examined.