MICROVASCULAR CONTROL--A ROLE FOR INTEGRINS

描述：(改编自应用程序)整合素是一种重要的 细胞表面受体家族，结合不溶的ECM蛋白和 转导参与细胞基本功能的细胞信号。一些人 整合素也作为可溶性配体的受体，如纤维蛋白原和 基质蛋白的碎片。已知的片段ECM蛋白是 在组织损伤过程中产生。调查人员推测，这些 片段充当独特的生物活性信号，能够改变 通过它们之间的相互作用来发挥微血管功能。他们提出，这些 ECM来源的信号可能在血管反应中发挥重要作用 受伤。初步研究表明，孤立的小动脉在 对含有RGD但不含RGE序列的多肽片段的反应。 这种扩张性反应不需要内皮细胞，似乎是 通过RGD与avb3的结合而介导。也观察到类似的扩张。 对已知的变性胶原蛋白水解物片段的反应 在组织损伤过程中产生的，这表明胶原可能作为一种 这些配体的活体来源。胶原蛋白，这是最丰富的基质 蛋白质，每个分子包含多个RGD序列。蛋白水解酶可能 理论上释放可溶的RGD或非RGD多肽，然后 与血管壁整合素相互作用。调查人员假设 ECM可以作为独特的RGD或不含RGD的多肽的来源 能够调节血管运动功能的。具体目标是：1) 分离小动脉和完整小动脉血管运动反应的特征 已知整合素结合肽和胶原的微血管制剂 片段；2)分离鉴定产生的活性多肽 从蛋白水解性变性的I型胶原中；以及3)鉴定 负责血管活动的细胞内信号通路。一种能力 整合素结合肽启动细胞功能变化并诱导 生理反应具有潜在的治疗意义，因为 整合素配体可能在操作血管功能和 对受伤的反应。

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.