PROTEOLYZED COLLAGEN IN ANGIOGENESIS AND APOPTOSIS

描述：（改编自研究者摘要）主要目的 该提案的目的是定义胶原蛋白降解的特定作用， 血管生成过程中的组织重塑。 调查员建议检查 间质蛋白水解修饰的功能意义 I型胶原是血管细胞外基质的主要成分， 在历史上被认为是调节组织的结构成分 形态发生和稳定性。 血管生成被认为依赖于 细胞粘附和蛋白水解机制。 然而，迄今为止， 已知细胞粘附受体和蛋白水解降解 细胞外基质（ECM）成分在细胞内协同作用， 调节体内血管生成。 潜在的细胞和生化 蛋白水解降解胶原蛋白的机制， 片段可以作为血管整联蛋白α V β 3的配体， 将检测增强内皮细胞存活和血管生成。 假设是基质金属蛋白酶（MMPs），主要的一类 能够特异性降解间质胶原蛋白的酶， 调节并选择性地与体内血管生成血管相关。 将确定升高水平的MMP是否在肿瘤细胞中表达。 蛋白水解活性形式，可以启动蛋白水解的 血管生成血液直接微环境中的间质胶原 船舶. 胶原蛋白的蛋白水解降解揭示 提供生理上重要的配体的隐蔽的粘附序列 对于连接所必需的血管整合素α v β 3介导的事件 内皮细胞存活和血管生成的影响。 以来 血管生成在各种正常和病理性的 过程，了解调节这一过程的分子事件是 这不仅对我们基本的理解， 血管生成，而且设计新的治疗策略， 以新生血管形成为特征的疾病 因此本研究 应该提供新的信息，以弥合我们在理解上的差距。 调节体内新血管形成的复杂机制， 提供了第一个证据，证明蛋白水解胶原蛋白在 内皮细胞存活和血管生成的调节。

DESCRIPTION: (adapted from the investigator's abstract) The major objective of this proposal is to define a specific role for collagen degradation and tissue remodeling during angiogenesis. The investigator proposes to examine the functional significance of proteolytic modification of interstitial collagen type-I, a major component of the vascular extracellular matrix that has historically been considered as a structural component regulating tissue morphogenesis and stability. Angiogenesis has been suggested to depend on both cell adhesion and proteolytic mechanisms. However, to date, little is known concerning how cell adhesion receptors and proteolytically degraded extracellular matrix (ECM) components function cooperatively in the regulation of angiogenesis in vivo. The potential cellular and biochemical mechanisms by which proteolytically degraded collagen and resulting fragments can function as a ligand for vascular integrin alphav beta3, potentiating endothelial cell survival and angiogenesis will be examined. The hypothesis is that matrix metalloproteinases (MMPs), the primary class of enzymes capable of specifically degrading interstitial collagen, are up regulated and selectively associated with angiogenic blood vessels in vivo. It will be determined whether the elevated levels of MMPs are expressed in a proteolytically active form that could initiate the formation of proteolyzed interstitial collagen in the immediate microenvironment of angiogenic blood vessels. The ability of proteolytic degradation of collagen to reveal cryptic adhesive sequences that provide a physiologically important ligand for vascular integrin alphav beta3-mediated event necessary for the ligation of endothelial cell survival and angiogenesis will be tested. Since angio-genesis plays a critical role in a variety of normal and pathological processes, understanding the molecular events that regulate this process is of paramount importance, not only to our basic understanding of angiogenesis, but also to the design of novel strategies for the treatment of diseases characterized by neovascularization. Therefore, this study should provide new information to bridge the gap in our understanding of the complex mechanisms that regulate new blood vessels formation in vivo and provide the first evidence for a specific role for proteolyzed collagen in the regulation of endothelial cell survival and angiogenesis.