MICROVASCULAR CONTROL--A ROLE FOR INTEGRINS

描述：（改编自应用程序）整合素是重要的 与不溶性ECM蛋白结合的细胞表面受体家族， 参与基本细胞功能的细胞信号。 一些 整联蛋白也作为可溶性配体如纤维蛋白原和 基质蛋白的片段。 已知片段化的ECM蛋白是 在组织损伤时产生。 研究人员推测，这些 片段作为独特的生物活性信号， 微血管通过它们的相互作用发挥功能。 他们建议，这些 ECM衍生的信号可能在血管对血管反应中起重要作用， 损伤 初步研究表明，孤立的小动脉扩张， 对含有RGD但不含RGE序列的肽片段的反应。 这种舒张反应不需要内皮细胞， 通过与avb 3结合的RGD介导。 观察到类似的扩张， 对变性胶原蛋白的蛋白水解片段的反应， 在组织损伤过程中产生，这表明胶原蛋白可能作为一种免疫抑制剂， 这些配体的体内来源。 胶原蛋白，这是最丰富的基质 蛋白质，每个分子含有多个RGD序列。 蛋白质水解可以 理论上释放可溶性RGD或非RGD肽， 与血管壁整合素相互作用。 研究人员假设， ECM可以作为独特含RGD或不含RGD的肽的来源 能够调节血管功能。 具体目标是：1） 表征孤立小动脉和完整小动脉的血管反应 已知的整合素结合肽和胶原的微血管制剂 2）分离并鉴定产生的活性肽 来自蛋白水解切割的变性I型胶原;和3）鉴定 负责血管活性的细胞内信号通路。 的能力 整合素结合肽，以启动细胞功能的变化， 生理反应具有潜在的治疗意义， 整联蛋白配体可用于操纵血管功能 对伤害的反应。

DESCRIPTION: (Adapted from the application) Integrins are an important family of cell surface receptors that bind to insoluble ECM proteins and transduce cell signals involved in fundamental cellular functions. Some integrins also act as receptors for soluble ligands, such as fibrinogen and fragments of matrix proteins. Fragmented ECM proteins are known to be generated during tissue injury. The investigators hypothesize that these fragments act as unique biologically active signals capable of altering microvascular functions through their interactions. They propose that these ECM-derived signals may play an important role in the vascular response to injury. The preliminary studies show that isolated arterioles dilate in response to peptide fragments containing the RGD but not the RGE sequence. This dilatory response does not require endothelium and appears to be mediated through RGD binding to avb3. Similar dilatation was observed in response to proteolytic fragments of denatured collagen known to be generated during tissue injury, suggesting that collagen may act as an in vivo source of these ligands. Collagens, which are the most abundant matrix proteins, contain multiple RGD sequences per molecule. Proteolysis could theoretically liberate soluble RGD or non-RGD peptides which could then interact with vascular wall integrins. The investigators hypothesize that the ECM can act as a source of unique RGD or non-RGD-containing peptides capable of regulating vasomotor function. The specific aims are: 1) Characterize the vasomotor response of isolated arterioles and intact microvascular preparations to known integrin binding peptides and collagen fragments; 2) Isolate and identify the active peptides that are generated from proteolytically cleaved denatured type I collagen; and 3) Identify intracellular signaling pathways responsible for vasoactivity. The ability of integrin binding peptides to initiate changes in cell function and elicit physiological responses is of potential therapeutic interest because integrin ligands may be useful in the manipulation of vascular function and the response to injury.