ROLE OF THE NEUROLOGIC SYSTEM IN CUTANEOUS ANGIOGENESIS

描述：（改编自申请人的摘要）-这是重新提交 一个竞争性的更新以前的建议，审查的作用， 神经系统在皮肤伤口愈合中的作用。在过去的融资中 期间，它被证明是皮肤感觉神经系统和 释放的神经肽能够调节许多重要的 皮肤中的炎症和伤口愈合反应的组分。这 应用程序将测试一般假设，即感觉神经系统是 能够调节皮肤血管生成的许多基本方面 通过释放神经肽如P物质（SP）和降钙素基因 相关肽（CGRP）。释放的神经肽激活特定的真皮 微血管内皮细胞（DMEC）神经肽受体促进 血管生成这种相互作用可能在调节正常和 皮肤中的病理过程。本申请的具体目的是： 1)确定特定感觉神经肽调节DMEC的能力 血管生成反应直接; 2）确定激活的神经突的能力 直接调节DMEC血管生成反应; 3）测定DMEC血管生成反应的能力。 皮肤神经系统以调节皮肤中的血管生成;以及4） 确定皮肤神经系统调节 在皮肤伤口愈合中的血管生成。特定神经肽的作用 以及它们各自的受体在调节血管生成中的作用将在 利用鼠和人模型系统进行体外和体内研究。体外 将通过测量微血管密度来评估DMEC血管生成反应。 内皮细胞（a）增殖，（B）趋化性/化学运动，（c）基质 金属蛋白酶（MMP）/MMP产生的组织抑制剂，（d）内皮细胞 细胞衍生的血管生成因子产生，和（e）内皮管 形成/发芽。共培养的激活的感觉神经元的能力 将确定诱导血管生成活性的DMEC。体内皮肤 局部辣椒素注射神经肽的血管生成反应，在正常 并且在伤口愈合期间将通过直接血管计数来测量， 免疫染色后的计算机辅助图像分析。这些研究将 进一步了解神经系统在血管生成中的作用 并可能为广泛的皮肤过程带来新的治疗方法 包括炎症、伤口愈合和瘤形成。

DESCRIPTION: (Adapted from the applicant's abstract) - This is a resubmission of a competitive renewal of a previous proposal that examined the role of the neurological system in cutaneous wound healing. During the previous funding period, it was demonstrated that the cutaneous sensory neurological system and released neuropeptides were capable of modulating a number of important components of inflammation and wound healing responses in the skin. This application will test the general hypothesis that the sensory nervous system is capable of regulating a number of essential aspects of cutaneous angiogenesis by the release of neuropeptides such as substance P (SP) and calcitonin gene related peptide (CGRP). The released neuropeptides activate specific dermal microvascular endothelial cell (DMEC) neuropeptide receptors to promote angiogenesis. This interaction might play a key role in modulating normal and pathological processes in the skin. The specific aims of this application are: 1) Determine the capacity of specific sensory neuropeptides to modulate DMEC angiogenic responses directly; 2) determine the capacity of activated neurites to modulate DMEC angiogenic responses directly; 3) determine the capacity of the cutaneous neurological system to modulate angiogenesis in the skin; and 4) determine the capacity of the cutaneous neurological system to modulate angiogenesis in wound healing of the skin. The role of specific neuropeptides and their respective receptors in modulating angiogenesis will be determined in vitro and in vivo utilizing both murine and human model systems. In vitro DMEC angiogenesis responses will be assessed by measuring microvascular endothelial cell (a) proliferation, (b) chemotaxis/ chemokinesis, (c) matrix metalloproteinase (MMP)/tissue inhibitor of MMP production, (d) endothelial cell derived angiogenic factor production, and (e) endothelial tube formation/sprouting. The ability of activated sensory neurons co-cultured with DMEC to induce angiogenic activities will be determined. In vivo cutaneous angiogenic responses to topical capsaicin, injected neuropeptides, in normal and during wound healing will be measured by direct vessel counts and computer-assisted image analysis after immunostaining. These studies will further basic understanding of the role of the nervous system in angiogenesis and could lead to novel therapies for a wide range of cutaneous processes including inflammation, wound healing, and neoplasia.