Extracellular Matrix in Mice Lacking Thrombospondin 2

描述（由申请人提供）：血小板反应蛋白2（TSP 2）是一种 调节细胞功能如粘附的细胞外蛋白， 迁移和增殖，通过其与生长因子相互作用的能力， 细胞因子、蛋白酶和大量的细胞表面受体。的小鼠 缺乏TSP 2显示出许多看似无关缺陷，包括异常的 结构化的胶原纤维，减少的成纤维细胞粘附，出血性疾病， 以及以血管分布增加为特征的对损伤的反应。的 这个建议的目的是了解这种多样的表型是如何产生的 因为缺乏单一的蛋白质。更重要的是，我们希望了解 更多关于蛋白酶在细胞粘附中的作用， 和骨生长，参与正常血小板形成的因素， 聚集和伤口愈合的过程。计划的实验包括：1） 基质金属蛋白酶MMP 2与TSP 2相互作用的研究， 细胞表面; 2）MMP 2在异物反应中的作用; 3）血小板 与内皮下的形成和相互作用; 4） 通过TSP 2抑制血管生成和骨生长，即通过细胞凋亡相对于通过 细胞增殖的抑制;和5）TSP表型的评价 1 /TSP 2双缺失小鼠，以及每种蛋白质缺失的贡献 与局部基因治疗确定的表型相匹配。这些实验 开发改善伤口愈合方法的潜力，以及 植入的生物传感器和输送装置的性能。

DESCRIPTION (provided by applicant): Thrombospondin 2 (TSP2) is an extracellular protein that modulates cell functions such as adhesion, migration, and proliferation by its ability to interact with growth factors, cytokines, proteases, and a large number of cell-surface receptors. Mice that lack TSP2 display a number of seemingly unrelated defects including abnormally structured collagen fibrils, reduced fibroblast adhesion, a bleeding disorder, and a response to injury that is characterized by increased vascularity. The purpose of this proposal is to understand how this diverse phenotype can result from the absence of a single protein. More fundamentally, we expect to learn more about the role of proteases in cell adhesion, the control of angiogenesis and bone growth, the factors involved in normal platelet formation and aggregation, and the course of wound healing. Planned experiments include: 1) studies of the interaction of a matrix metalloproteinase, MMP2, with TSP2 and the cell surface; 2) the role of MMP2 in the foreign body response; 3) platelet formation and interaction with the sub-endothelium; 4) the mechanism of inhibition of angiogenesis and bone growth by TSP2, i.e. by apoptosis versus by inhibition of cell proliferation; and 5) an evaluation of the phenotype of TSP 1 /TSP2 double-null mice, and of the contribution of the lack of each protein to the phenotype as determined by local gene therapy. These experiments have the potential to develop the means to improve wound healing, and the performance of implanted biosensors and delivery devices, in human subjects.