EPIDERMAL GROWTH FACTOR STIMULATES WOUND HEALING IN VIVO

描述：(改编自申请人的摘要)维护正常 皮肤功能仍然是人类日常面临的挑战，因为这一障碍 在不断的攻击下，无论是计划外的(创伤，烧伤，病原体， 紫外线照射、缺血、环境毒素)和计划(手术)。这 该提案旨在检查由 皮肤试图维持动态平衡。定义伤口反应 创伤后，沿表皮的关键信号转导反应 AIM I将在体外检测生长因子受体途径 角质形成细胞创伤模型具有可预测的迁移、增殖和 分化角质形成细胞，模拟上皮化阶段 伤口修复。这个模型系统应该被证明是有用的信号解剖 从这个原型下游激活的转导步骤 酪氨酸激酶受体(EGF-R)。角质形成细胞将被转基因 突变的EGF-R形成显性阴性EGF-R角质形成细胞。 EGF-R介导的信号转导通路的可能改变 应该为激活的生长控制机制提供有价值的线索 皮肤伤口愈合。关于EGF-R酪氨酸的重要发现 在人类烧伤和慢性创面中，将进一步探索激酶途径。 在AIM II中，信号转导反应将使用猪的IN来定义 活体创伤模型。EGF-R基因在急性白血病中的表达 用RT-PCR技术检测伤期。可能的差异效应 经过外源性治疗的各种EGF样配体将被 在部分厚度损伤模型和移植物全厚度损伤模型中进行了探索。 最后，猪的伤口修复参数将使用基因进行操作 心理治疗。将采取策略来提高受体水平，以实现这一目标 实现方便维修的目标。生长因子/细胞因子机制 控制皮肤移植后的一过性生长和增殖 伤害仍然是这项提议的中心焦点。的主要目标是 这个建议是为了研究EGF-R相关的信号通路，以帮助 创面修复新疗法的设计。

DESCRIPTION: (Adapted from the applicant's abstract) Maintenance of normal cutaneous function remains a daily challenge to humans since this barrier is under constant assault, both unplanned (trauma, burns, pathogenic organisms, UV exposure, ischemia, environmental toxins) and planned (surgery). This proposal is designed to examine cutaneous growth control mechanisms used by the skin in its attempt to maintain homeostasis. To define wound responses following trauma, key signal transduction responses along the epidermal growth factor receptor pathway will be examined in Aim I in an in vitro keratinocyte wound model with predictable migrating, proliferating, and differentiating keratinocytes that mimic the reepithelialization phase of wound repair. This model system should prove useful for dissecting signal transduction steps that are activated downstream from this prototype tyrosine kinase receptor (EGF-R). Keratinocytes will be transfected with mutant EGF-R forms to achieve dominant negative EGF-R keratinocytes. Possible alterations to the EGF-R mediated signal transduction pathway should yield valuable clues into growth control mechanisms activated in cutaneous wound healing. Significant findings along the EGF-R tyrosine kinase pathway will be further explored in human burns and chronic wounds. In Aim II, signal transduction responses will be defined using porcine in vivo wound models. EGF-R gene expression will be followed in the acute wound period using RT-PCR techniques. Possible differential effects following exogenous treatment from a variety of EGF like ligands will be explored in partial-thickness and grafted full-thickness injury models. Lastly, porcine wound repair parameters will be manipulated using gene therapy. Strategies will be employed to boost receptor levels with the goal of achieving facilitated repair. Growth factor/cytokine mechanisms controlling the transient growth and proliferation following cutaneous injury continue to be the central focus of this proposal. The prime goal of this proposal is to examine EGF-R associated signaling pathways to aid in the design of new therapies for wound repair.